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Borrero‐Garcia LD, Moró‐Carrión M, Torres‐Cintrón CR, Centeno‐Girona H, Perez V, Santos‐Colón T, González‐Pons M. Disparities in Colorectal Cancer Incidence Trends Among Hispanics Living in Puerto Rico (2000-2021): A Comparison With Surveillance, Epidemiology, and End Results (SEER) Database. Cancer Med 2025; 14:e70851. [PMID: 40249262 PMCID: PMC12007180 DOI: 10.1002/cam4.70851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 02/25/2025] [Accepted: 03/25/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Although the overall colorectal cancer (CRC) incidence has been steadily declining in the United States, a dramatic increase in the number of CRC cases among individuals younger than 50 years of age (early-onset CRC) has been observed. CRC is the second and first leading cause of cancer death in the United States and among Hispanic men and women living in Puerto Rico (PRH), respectively. We report CRC incidence rates from 2000 to 2021 among PRH and compare them to data in the Surveillance, Epidemiology, and End Results Program (SEER). METHODS Data on colorectal adenocarcinomas diagnosed between January 1, 2000, and December 31, 2021, were obtained from the Puerto Rico Central Cancer Registry and SEER17, including race and ethnicity. Age-standardized incidence rates were calculated using the direct method. The Joinpoint Regression Program calculated temporal trends on CRC incidence rates based on age-adjusted Average Annual Percent Change (AAPC) estimates. RESULTS A total of 729,479 incident cases of CRC were analyzed. US Hispanics had the highest percentage of early-onset CRC (EOCRC) cases (17.0%) among the racial and ethnic groups studied. PRH had the highest age-standardized EOCRC incidence rate (12.18 per 100,000 persons) and the highest increase in EOCRC incidence temporal trends (AAPC = 2.68; 95% CI: 1.83 to 3.51). CONCLUSIONS A significantly higher increase in EOCRC incidence was observed among Hispanic populations. Future studies should disaggregate Hispanic subpopulations by considering the country of ancestral origin, which will help identify specific risk factors and exposures and aid in developing tailored prevention and risk stratification strategies to reduce EOCRC incidence.
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Affiliation(s)
- Luis D. Borrero‐Garcia
- Division of Clinical and Translational Cancer ResearchUniversity of Puerto Rico Comprehensive Cancer CenterSan JuanPuerto Rico
| | - Marilyn Moró‐Carrión
- Division of Clinical and Translational Cancer ResearchUniversity of Puerto Rico Comprehensive Cancer CenterSan JuanPuerto Rico
| | | | - Hilmaris Centeno‐Girona
- Division of Clinical and Translational Cancer ResearchUniversity of Puerto Rico Comprehensive Cancer CenterSan JuanPuerto Rico
| | - Victoria Perez
- School of Public HealthUniversity of Texas Health Science Center HoustonDallasTexasUSA
| | | | - María González‐Pons
- Division of Clinical and Translational Cancer ResearchUniversity of Puerto Rico Comprehensive Cancer CenterSan JuanPuerto Rico
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Gong M, Xia T, Chen Z, Zhu Y. Comparison analysis of the burden and attributable risk factors of early-onset and late-onset colorectal cancer in China from 1990 to 2019. Eur J Cancer Prev 2025; 34:140-150. [PMID: 39150077 DOI: 10.1097/cej.0000000000000907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
OBJECTIVES The project intended to analyze the impact of burden and related risk factors of late-onset colorectal cancer (LOCRC) and early-onset colorectal cancer (EOCRC) in China, thus offering essential references for optimizing prevention and control strategies. METHOD Global Burden of Disease Study was employed to describe burden changes of EOCRC and LOCRC in China during 1990-2019, containing the numbers of incidence, deaths, prevalence, and disability-adjusted life years (DALYs), and to compare attributable deaths and DALYs risk factors in varying age and sex segments. RESULTS The numbers and corresponding crude rates of incidence, deaths, prevalence, and DALYs of EOCRC and LOCRC in China during 1990-2019 demonstrated an upward trend across all age categories, with males being dramatically predominant. Overall, over time, the impact of a low-calcium diet and a low-fiber diet on mortality and DALY rates decreased, while the impact of other risk factors increased. In terms of gender, the risk factors affecting males changed greatly, with smoking, inadequate milk intake, and the low whole-grain diet being the main factors in 2019, while in 1990, the main factors were the low-calcium diet, smoking, and inadequate milk intake. CONCLUSION The burden of colorectal cancer in China is concerning. Patients grouped by diagnostic age exhibit different characteristics, indicating the need for high-quality research in the future to achieve personalized medicine tailored to different population characteristics.
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Affiliation(s)
| | - Tian Xia
- Department of Colorectal Surgery
| | | | - Yuanyuan Zhu
- Department of Oncology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China
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Le NT, Pham YTH, Le LT, Dao HV, Koriyama C, Ha TH, Lichtveld M, Kuchipudi SV, Huynh NYN, Nguyen DD, Luu HN. Factors Affecting Cancer Mortality in Young Adults: Findings from a Prospective Cohort Study. Cancers (Basel) 2024; 16:3853. [PMID: 39594808 PMCID: PMC11593055 DOI: 10.3390/cancers16223853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/09/2024] [Accepted: 11/13/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Cancer incidence in young adults or those aged 15-49 years old has increased during the past decade. Knowledge about the risk factors for cancer-related deaths in young adults is limited, particularly in low- and middle-income countries (LMICs). METHODS This analysis was based on the Hanoi Prospective Cohort Study, an ongoing study of 39,401 participants aged 15 or older in Northern Vietnam in the 2007-2019 period. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence intervals (95% CIs) for the association between potential factors and the risk of cancer-related deaths. RESULTS With a median follow-up of 11.01 years, we identified 164 deaths in young adults out of 554 total deaths. Overall, family history of cancer (HR = 7.34; 95% CI: 3.30-16.36), drinking alcohol (HR = 1.82; 95% CI: 1.18-2.81), and smoking (HR = 2.22; 95% CI: 1.36-3.63) were found to be risk factors, while drinking coffee was found to be a protective factor (HR = 0.49; 95% CI: 0.24-1.00) for cancer-related deaths in young adults. Young male adults were found to be at a higher risk due to excessive cigarette smoking (HR = 1.91; 95% CI: 1.00-3.68) and alcohol consumption (HR = 2.15; 95% CI: 1.32-3.53) than those aged 50 years and older (HR = 1.36 and 95% CI: 0.96-1.93 and 1.27 and 95% CI: 0.97-1.67, respectively). The risk of death from cancer in women compared with men in the young population was twice as high as that in the older population (HR = 1.18 and 95% CI: 0.72-1.94 vs. 0.47 and 95% CI: 0.35-0.63, respectively). CONCLUSIONS Our data suggest that the young Vietnamese population is vulnerable to the risk of cancer-related deaths and that cancer in women will increase rapidly in the future.
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Affiliation(s)
- Ngoan T. Le
- Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam
- Department of Occupational Health, Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi 100000, Vietnam
| | - Yen T.-H. Pham
- University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA 15261, USA;
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
| | - Linh T. Le
- Laboratory of Embryology and Genetics of Human Malformation, Imagine Institute, INSERM UMR, 59045 Paris, France;
| | - Hang V. Dao
- Internal Medicine Faculty, Hanoi Medical University, Hanoi 100000, Vietnam;
| | - Chihaya Koriyama
- Department of Epidemiology and Preventive Medicine, Graduate School of Medicine and Dental Science, Kagoshima University, Kagoshima 890-0065, Japan;
| | - Toan H. Ha
- Department of Infectious Disease and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA; (T.H.H.); (S.V.K.)
| | - Maureen Lichtveld
- Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA;
| | - Suresh V. Kuchipudi
- Department of Infectious Disease and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA; (T.H.H.); (S.V.K.)
| | - Nhi Y.-N. Huynh
- School of Medicine, International University of Health and Welfare, Narita 324-8501, Japan; (N.Y.-N.H.); (D.D.N.)
| | - Dai D. Nguyen
- School of Medicine, International University of Health and Welfare, Narita 324-8501, Japan; (N.Y.-N.H.); (D.D.N.)
| | - Hung N. Luu
- University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA 15261, USA;
- Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
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Ungvari Z, Fekete M, Varga P, Lehoczki A, Fekete JT, Ungvari A, Győrffy B. Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk. GeroScience 2024:10.1007/s11357-024-01375-x. [PMID: 39379738 DOI: 10.1007/s11357-024-01375-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 10/01/2024] [Indexed: 10/10/2024] Open
Abstract
The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case-control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24-1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38-1.78, p = 0.01) for males and 1.25 (95% CI = 1.14-1.38, p < 0.01) for females. Case-control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98-1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case-control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case-control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer.
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Affiliation(s)
- Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
| | - Mónika Fekete
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - Peter Varga
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - Andrea Lehoczki
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - János Tibor Fekete
- Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary
| | - Anna Ungvari
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary.
| | - Balázs Győrffy
- Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary
- Dept. of Biophysics, Medical School, University of Pecs, 7624, Pecs, Hungary
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Wang Y, Wu ZL, Wang YG, Wang H, Jia XY. Early colorectal cancer screening–no time to lose. World J Gastroenterol 2024; 30:2959-2963. [PMID: 38946873 PMCID: PMC11212702 DOI: 10.3748/wjg.v30.i23.2959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 05/15/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
In this editorial, we comment on the article entitled “Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?” by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.
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Affiliation(s)
- Ying Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 310018, Zhejiang Province, China
| | - Zheng-Long Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Yi-Gang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Hui Wang
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 310018, Zhejiang Province, China
| | - Xiao-Yuan Jia
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
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Wang Z, Yao W, Wu W, Huang J, Ma Y, Yang C, Shi J, Fu J, Wang Y, Wong MCS, Xu W. Global incidence trends of early-onset colorectal cancer and related exposures in early-life: an ecological analysis based on the GBD 2019. Front Public Health 2024; 12:1367818. [PMID: 38966706 PMCID: PMC11222603 DOI: 10.3389/fpubh.2024.1367818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 06/11/2024] [Indexed: 07/06/2024] Open
Abstract
Background The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019. Methods Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC. Results The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years. Conclusion The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.
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Affiliation(s)
- Ziyang Wang
- Global Health Institute, Fudan University School of Public Health, Shanghai, China
| | - Weiyuan Yao
- Global Health Institute, Fudan University School of Public Health, Shanghai, China
| | - Weimiao Wu
- Global Health Institute, Fudan University School of Public Health, Shanghai, China
| | - Junjie Huang
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China
| | - Yanlei Ma
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Chen Yang
- Centre for Disease Control & Prevention in Pudong New Area of Shanghai, Shanghai, China
| | - Jufang Shi
- Office of Cancer Screening, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiongxing Fu
- Global Health Institute, Fudan University School of Public Health, Shanghai, China
| | - Yingying Wang
- Centre for Disease Control & Prevention in Pudong New Area of Shanghai, Shanghai, China
| | - Martin C. S. Wong
- Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China
| | - Wanghong Xu
- Global Health Institute, Fudan University School of Public Health, Shanghai, China
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Yuan C, Shu X, Hu Z, Jie Z. Genetic prediction of the relationship between metabolic syndrome and colorectal cancer risk: a Mendelian randomization study. Diabetol Metab Syndr 2024; 16:109. [PMID: 38773583 PMCID: PMC11110320 DOI: 10.1186/s13098-024-01351-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/15/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND Despite a growing body of observational studies indicating a potential link between metabolic syndrome and colorectal cancer, a definitive causal relationship has yet to be established. This study aimed to elucidate the causal relationship between metabolic syndrome and colorectal cancer through Mendelian randomization. METHODS We screened for instrumental variables associated with metabolic syndrome and its diagnostic components and with colorectal cancer through the use of a genome-wide association study database, and conducted a preliminary Mendelian randomization analysis. To corroborate the dependability of our conclusions, an additional dataset was used for replication analysis in a Mendelian randomization method, which was further integrated with a meta-analysis. RESULTS Preliminary analysis using the inverse variance weighted method revealed positive correlations between metabolic syndrome (OR [95% CI] = 1.37[1.15-1.63], P = 5.02 × 10-4) and waist circumference (OR [95% CI] = 1.39[1.21-1.61], P = 7.38 × 10-6) and the risk of colorectal cancer. Replication analysis also revealed the same results: metabolic syndrome (OR [95% CI] = 1.24[1.02-1.51], P = 0.030) and waist circumference (OR [95% CI] = 1.23[1.05-1.45], P = 0.013). The meta-analysis results further confirmed the associations between metabolic syndrome (OR [95% CI] = 1.31[1.15-1.49], P < 0.001) and waist circumference (OR [95% CI] = 1.32[1.18-1.47], P < 0.001) and colorectal cancer. CONCLUSION Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.
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Affiliation(s)
- Chendong Yuan
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Xufeng Shu
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Zhenzhen Hu
- Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Zhigang Jie
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
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Xu P, Tao Z, Yang H, Zhang C. Obesity and early-onset colorectal cancer risk: emerging clinical evidence and biological mechanisms. Front Oncol 2024; 14:1366544. [PMID: 38764574 PMCID: PMC11100318 DOI: 10.3389/fonc.2024.1366544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 04/22/2024] [Indexed: 05/21/2024] Open
Abstract
Early-onset colorectal cancer (EOCRC) is defined as diagnosed at younger than 50 years of age and indicates a health burden globally. Patients with EOCRC have distinct risk factors, clinical characteristics, and molecular pathogenesis compared with older patients with CRC. Further investigations have identified different roles of obesity between EOCRC and late-onset colorectal cancer (LOCRC). Most studies have focused on the clinical characteristics of obesity in EOCRC, therefore, the mechanism involved in the association between obesity and EOCRC remains inconclusive. This review further states that obesity affects the carcinogenesis of EOCRC as well as its development and progression, which may lead to obesity-related metabolic syndrome, intestinal dysbacteriosis, and intestinal inflammation.
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Affiliation(s)
- Peng Xu
- Department of General Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Zuo Tao
- Department of General Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Hua Yang
- Department of General Surgery, Xinqiao Hospital, Army Medical University, Third Military Medical University, Chongqing, China
| | - Cheng Zhang
- Department of General Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
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Demb J, Kolb JM, Dounel J, Fritz CDL, Advani SM, Cao Y, Coppernoll-Blach P, Dwyer AJ, Perea J, Heskett KM, Holowatyj AN, Lieu CH, Singh S, Spaander MCW, Vuik FER, Gupta S. Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open 2024; 7:e2413157. [PMID: 38787555 PMCID: PMC11127127 DOI: 10.1001/jamanetworkopen.2024.13157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 03/19/2024] [Indexed: 05/25/2024] Open
Abstract
IMPORTANCE Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. OBJECTIVE To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. DATA SOURCES PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. STUDY SELECTION Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. DATA EXTRACTION AND SYNTHESIS Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. RESULTS Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). CONCLUSIONS AND RELEVANCE In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.
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Affiliation(s)
- Joshua Demb
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Jennifer M. Kolb
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, California
| | - Jonathan Dounel
- Department of Medicine, University of California San Diego, La Jolla
| | | | - Shailesh M. Advani
- Department of Internal Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri
| | | | - Andrea J. Dwyer
- University of Colorado Cancer Center, Colorado School of Public Health, Aurora
| | - Jose Perea
- Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, Spain
- Surgery Department, Vithas Arturo Soria University Hospital, Madrid, Spain
| | - Karen M. Heskett
- UC San Diego Library, University of California San Diego, La Jolla
| | - Andreana N. Holowatyj
- Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Christopher H. Lieu
- Division of Medical Oncology, University of Colorado Denver Anschutz Medical Campus, Aurora
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Manon C. W. Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Fanny E. R. Vuik
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Samir Gupta
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
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10
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Oliveira ML, Biggers A, Oddo VM, Yanez B, Booms E, Sharp L, Naylor K, Wolf PG, Tussing-Humphreys L. A Perspective Review on Diet Quality, Excess Adiposity, and Chronic Psychosocial Stress and Implications for Early-Onset Colorectal Cancer. J Nutr 2024; 154:1069-1079. [PMID: 38453027 PMCID: PMC11007745 DOI: 10.1016/j.tjnut.2024.03.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 02/23/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Although the overall incidence of CRC has been decreasing over the past 40 y, early-onset colorectal cancer (EOCRC), which is defined as a CRC diagnosis in patients aged >50 y has increased. In this Perspective, we highlight and summarize the association between diet quality and excess adiposity, and EOCRC. We also explore chronic psychosocial stress (CPS), a less investigated modifiable risk factor, and EOCRC. We were able to show that a poor-quality diet, characterized by a high intake of sugary beverages and a Western diet pattern (high intake of red and processed meats, refined grains, and foods with added sugars) can promote risk factors associated with EOCRC development, such as an imbalance in the composition and function of the gut microbiome, presence of chronic inflammation, and insulin resistance. Excess adiposity, particularly obesity onset in early adulthood, is a likely contributor of EOCRC. Although the research is sparse examining CPS and CRC/EOCRC, we describe likely pathways linking CPS to tumorigenesis. Although additional research is needed to understand what factors are driving the uptick in EOCRC, managing body weight, improving diet quality, and mitigating psychosocial stress, may play an important role in reducing an individual's risk of EOCRC.
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Affiliation(s)
- Manoela Lima Oliveira
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States.
| | - Alana Biggers
- College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Vanessa M Oddo
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
| | - Betina Yanez
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Emily Booms
- Department of Biology, Northeastern Illinois University, Chicago, IL, United States
| | - Lisa Sharp
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, IL, United States
| | - Keith Naylor
- College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Patricia G Wolf
- Department of Nutrition Science, Purdue University, West Lafayette, IN, United States
| | - Lisa Tussing-Humphreys
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
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11
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Gupta S, May FP, Kupfer SS, Murphy CC. Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice. Clin Gastroenterol Hepatol 2024; 22:455-469.e7. [PMID: 38081492 PMCID: PMC11304405 DOI: 10.1016/j.cgh.2023.11.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/21/2023] [Accepted: 11/28/2023] [Indexed: 01/06/2024]
Abstract
Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age <50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals aged 50 to 54 years, and flattening of prior decreasing incidence among individuals aged 55 to 74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity-including and extending beyond rising EOCRC-can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology.
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Affiliation(s)
- Samir Gupta
- Section of Gastroenterology, Jennifer Moreno San Diego VA Medical Center, San Diego, California; Division of Gastroenterology, Department of Medicine, and Moores Cancer Center, University of California, La Jolla, California.
| | - Folasade P May
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California; Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California; UCLA Kaiser Permanente Center for Health Equity, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Sonia S Kupfer
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, Illinois
| | - Caitlin C Murphy
- Department of Health Promotion & Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth Houston) School of Public Health, Houston, Texas
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12
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Isah Tsamiya R, Mohd Nafi SN, Che Jalil NA, Mat Zin AA. The Clinicopathological Characteristics of Young-Onset Versus Adult-Onset Colorectal Cancer: A Tertiary Hospital-Based Study. Malays J Med Sci 2024; 31:200-211. [PMID: 38456100 PMCID: PMC10917589 DOI: 10.21315/mjms2024.31.1.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 06/02/2023] [Indexed: 03/09/2024] Open
Abstract
Background The prevalence of colorectal cancer (CRC) among young individuals is rising worldwide, especially in Malaysia. Investigations are currently employed to distinguish the features of young-onset CRC (YOCRC) from adult-onset CRC (AOCRC). This study aimed to compare the characteristics of patients with YOCRC and AOCRC diagnosed at Hospital Universiti Sains Malaysia (HUSM). Methods This was a retrospective study of CRC cases from January 2013 to December 2021. The details of YOCRC (< 50 years old) and AOCRC (≥ 50 years old) patients were retrieved from the laboratory system and medical records. The Pearson's chi-square test, Fisher's exact test and multiple logistic regression were used to compare the AOCRC and YOCRC cases. Statistical significance was defined at a P-value of ≤ 0.05. Results The AOCRC (254/319, 79.6%) was more prevalent than YOCRC (65/319, 20.4%), with a predominance of males (53.9%) and Malay sub-population (90.2%). AOCRC and YOCRC shared similarities in left-sided location, high occurrence of adenocarcinoma with moderately differentiated histology and advanced stage of diagnosis. More patients with YOCRC (23.1%) had a family history of cancer than patients with AOCRC. YOCRC also differed from AOCRC by having more specific histological subtypes, such as mucinous adenocarcinoma (15.4%) and signet ring carcinoma (6.2%). In addition, patients with YOCRC commonly presented with a low density of tumour-infiltrating lymphocytes (TILs) (60%). Multiple logistic regression showed a family history of CRC (adjusted odds ratio [AOR] = 3.75, P = 0.003) and histological type (AOR = 15.21, P < 0.001) are more likely to cause YOCRC than diabetes (AOR = 0.06, P < 0.001) and hypertension (AOR = 0.14, P < 0.001) comorbidities, which are associated with AOCRC. Conclusion Our descriptive study presented the epidemiological and histopathological characteristics of AOCRC and YOCRC in HUSM, providing current information on distinguishing features between the groups.
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Affiliation(s)
- Rilwanu Isah Tsamiya
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Siti Norasikin Mohd Nafi
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nur Asyilla Che Jalil
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Hospital Universiti Sains Malaysia, Kelantan, Malaysia
| | - Anani Aila Mat Zin
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
- Hospital Universiti Sains Malaysia, Kelantan, Malaysia
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13
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Hameed H, Faheem S, Zaman M, Khan MA, Ghumman SA, Sarwar HS, Mahmood A. Multiomics approaches in cancer. BIOLOGICAL INSIGHTS OF MULTI-OMICS TECHNOLOGIES IN HUMAN DISEASES 2024:53-72. [DOI: 10.1016/b978-0-443-23971-7.00003-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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14
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He TC, Li JA, Xu ZH, Chen QD, Yin HL, Pu N, Wang WQ, Liu L. Biological and clinical implications of early-onset cancers: A unique subtype. Crit Rev Oncol Hematol 2023; 190:104120. [PMID: 37660930 DOI: 10.1016/j.critrevonc.2023.104120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/30/2023] [Indexed: 09/05/2023] Open
Abstract
In recent years, the incidence of cancers is continuously increasing in young adults. Early-onset cancer (EOC) is usually defined as patients with cancers under the age of 50, and may represent a unique subgroup due to its special disease features. Overall, EOCs often initiate at a young age, present as a better physical performance but high degree of malignancy. EOCs also share common epidemiological and hereditary risk factors. In this review, we discuss several representative EOCs which were well studied previously. By revealing their clinical and molecular similarities and differences, we consider the group of EOCs as a unique subtype compared to ordinary cancers. In consideration of EOC as a rising threat to human health, more researches on molecular mechanisms, and large-scale, prospective clinical trials should be carried out to further translate into improved outcomes.
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Affiliation(s)
- Tao-Chen He
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian-Ang Li
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhi-Hang Xu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qiang-Da Chen
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Han-Lin Yin
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ning Pu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Liang Liu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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15
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Obadina D, Haider H, Micic D, Sakuraba A. Older Age at First Screening Colonoscopy is Associated With an Increased Risk of Colorectal Adenomas and Cancer. J Clin Gastroenterol 2023; 57:804-809. [PMID: 35997687 DOI: 10.1097/mcg.0000000000001751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/08/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The goal of colorectal cancer (CRC) screening is to detect precancerous polyps before cancer development or identification of cancer at an early stage. Guidelines have recommended screening colonoscopy to start at age 45. Our aim was to determine the impact of delays in performing the first screening colonoscopy on the risk of adenoma or CRC detection. METHODS We analyzed colonoscopy and histopathology data of average CRC risk patients who had their first screening colonoscopy between 2010 and 2017. Univariate and multivariable logistic regression was performed to determine the association between demographic variables and the risk of adenomas or CRC. RESULTS A total of 1155 average risk patients underwent their initial screening colonoscopy during the study period. Median age was 54 years (range of 45-87) and 58.2% were females. In multivariable analysis, older age at first screening colonoscopy was significantly associated with the detection of adenomatous polyps (odds ratio 1.05, 95% confidence interval 1.04-1.07, P <0.001) and CRC (odds ratio 1.11, 95% confidence interval 1.06-1.16, P <0.001). The association between age and risk of adenomatous polyps (F-test 35.43, P =0.0019) and CRC (F-test 36.94, P =0.0017) fit an exponential growth model. It was estimated that the detection rate doubled every 14.20 years and 4.75 years for adenomas and CRC, respectively. CONCLUSION We found that older age at the initial performance of a screening colonoscopy was associated with increased detection of adenomatous polyps and CRC. This work highlights the need for guideline adherence for the prevention of CRC development.
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Affiliation(s)
- David Obadina
- Pritzker School of Medicine, The University of Chicago
| | - Haider Haider
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, IL
| | - Dejan Micic
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, IL
| | - Atsushi Sakuraba
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, IL
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16
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Mohy-Ud-Din N, Syed A, Strahotin C, Babich M. Predictors and Outcomes of Palliative Care Consultations for Patients With Liver Disease: Results of a Cohort Study of 75 Million Medical Records. Am J Hosp Palliat Care 2023; 40:994-998. [PMID: 36655588 DOI: 10.1177/10499091231152229] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Background: Liver transplant is the only cure for cirrhosis. We studied the impact of palliative care on patient care by conducting a population-based cohort study. Methods: We queried the Explorys database (IBM, New York) database for a diagnosis of 'cirrhosis' followed by 'palliative care consultation' and collected demographic and clinical data. Results: We identified 316,970 patients with cirrhosis. Palliative care was consulted for 10.9% (n = 34,600) of patients. Patients aged >65 [OR 1.33 (1.30-1.36), P < .0001], men [OR 1.13 (1.11-1.16), P < .0001], a diagnosis of hepatocellular carcinoma (HCC) [OR 2.53 (2.45-2.60), P < .0001] were more likely to receive a palliative care consultation. Patients for whom palliative care were consulted were less likely to undergo surgical procedures [OR .49 (.47-.50)]. Conclusion: Only about 1 in 10 cirrhotics received a palliative care consultation. Older patients, males, and patients with a diagnosis of HCC are more likely to receive palliative care.
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Affiliation(s)
- Nabeeha Mohy-Ud-Din
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aslam Syed
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
- Department of Medicine, Case Western Reserve University/MetroHealth Medical Center, Cleveland, OH, USA
| | - Cristina Strahotin
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
| | - Michael Babich
- Division of Gastroenterology, Hepatology and Nutrition, Allegheny Health Network, Pittsburgh, PA, USA
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17
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Jin EH, Han K, Shin CM, Lee DH, Kang SJ, Lim JH, Choi YJ. Sex and Tumor-Site Differences in the Association of Alcohol Intake With the Risk of Early-Onset Colorectal Cancer. J Clin Oncol 2023; 41:3816-3825. [PMID: 37315287 PMCID: PMC10419447 DOI: 10.1200/jco.22.01895] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 03/28/2023] [Accepted: 05/03/2023] [Indexed: 06/16/2023] Open
Abstract
PURPOSE Given the increasing incidence of early-onset colorectal cancer (CRC; diagnosed before age 50 years) worldwide, it is important to identify modifiable risk factors. We investigated whether alcohol consumption in the young population correlated with an increased early-onset CRC risk that differed by tumor location and sex. PATIENTS AND METHODS We investigated the association between average daily alcohol consumption and the risk of early-onset CRC among 5,666,576 individuals age 20-49 years using data from the Korean National Health Insurance Service (2009-2019). Alcohol consumption levels of nondrinker, light (reference), moderate, and heavy drinker were defined as 0, <10, 10 to <30, and ≥30 g/d for men and 0, <10, 10 to <20, and ≥20 g/d for women, respectively. Multivariate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs. RESULTS We identified 8,314 incident early-onset CRC cases during the follow-up period. Moderate and heavy drinkers showed an increased risk of early-onset CRC compared with light drinkers (aHR, 1.09 [95% CI, 1.02 to 1.16] and aHR, 1.20 [95% CI, 1.11 to 1.29], respectively). Subgroup analysis by tumor location showed positive dose-response significance for early-onset distal colon and rectal cancers, but not for proximal colon cancer. The dose-response association between drinking frequency and risk of early-onset CRC was significant, with a 7%, 14%, and 27% increased risk for 1-2, 3-4, and ≥5 d/wk compared with nondrinkers, respectively. CONCLUSION Excessive alcohol consumption increases the risk of CRC onset before age 50 years. Thus, effective interventions are required to discourage alcohol consumption among young people and to tailor CRC screening approaches for high-risk individuals.
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Affiliation(s)
- Eun Hyo Jin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea
| | - Joo Hyun Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, South Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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18
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O'Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, Forbes N, Heitman SJ, Hilsden RJ, Brenner DR. Reply. Clin Gastroenterol Hepatol 2023; 21:1671-1672. [PMID: 36064099 DOI: 10.1016/j.cgh.2022.08.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Dylan E O'Sullivan
- Department of Community Health Sciences, University of Calgary; Department of Oncology, University of Calgary; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, Alberta, Canada
| | - R Liam Sutherland
- Department of Community Health Sciences, University of Calgary; Department of Oncology, University of Calgary; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, Alberta, Canada
| | - Susanna Town
- Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, Alberta, Canada
| | - Kristian Chow
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Jeremy Fan
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Nauzer Forbes
- Department of Community Health Sciences, University of Calgary; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Steven J Heitman
- Department of Community Health Sciences, University of Calgary; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Robert J Hilsden
- Department of Community Health Sciences, University of Calgary; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Darren R Brenner
- Department of Community Health Sciences, University of Calgary; Department of Oncology, University of Calgary; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, Alberta, Canada
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Bleyer A. Increasing Cancer in Adolescents and Young Adults: Cancer Types and Causation Implications. J Adolesc Young Adult Oncol 2023; 12:285-296. [PMID: 37074337 DOI: 10.1089/jayao.2022.0134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023] Open
Abstract
Purpose: This study aimed to identify cancer incidence trends in the United States and globally in adolescents and young adults (AYAs) 15-39 years of age, by sex, and to speculate on causes for trend changes. Methods: For the United States, SEER*Stat was used to obtain average annual percent change (AAPC) trends in cancer incidence during the period 2000-2019 among 395,163 AYAs. For global data, the source was the Institute of Health Metrics and Evaluation and its sociodemographic index (SDI) classification system. Results: In the United States, the invasive cancer incidence increased during the period 2000-2019 in both females (AAPC: 1.05, 95% CI: 0.90-1.20, p << 0.001) and males (AAPC: 0.56, 95% CI: 0.43-0.69, p << 0.001). A total of 25 and 20 types of cancers increased statistically significantly in female and male AYAs, respectively. Among potential causes for the increases, the obesity epidemic in the United States strongly correlates with the overall cancer increase in both its female (Pearson correlation coefficient R2 = 0.88, p = 0.0007) and male (R2 = 0.83, p = 0.003) AYAs, as does the most common malignancy in American AYAs, breast cancer (R2 = 0.83, p = 0.003). Worldwide, cancer incidence in the age group increased steadily during the period 2000-2019 among high-middle, middle, and low-middle SDI countries, but not in low SDI countries and with slowing of increase in high SDI countries. Conclusions: The increases and their age-dependent profiles implicate several causations that are preventable, including obesity, overdiagnosis, unnecessary diagnostic radiation, human papilloma virus infection, and cannabis avoidance. The United States is beginning to reverse the increasing incidence, and prevention efforts should be augmented accordingly.
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Affiliation(s)
- Archie Bleyer
- Pediatric & Young Adult Oncology, Oregon Health & Science University, Bend, Oregon, USA
- McGovern Medical School, University of Texas, Houston, Texas, USA
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20
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Spaander MCW, Zauber AG, Syngal S, Blaser MJ, Sung JJ, You YN, Kuipers EJ. Young-onset colorectal cancer. Nat Rev Dis Primers 2023; 9:21. [PMID: 37105987 PMCID: PMC10589420 DOI: 10.1038/s41572-023-00432-7] [Citation(s) in RCA: 114] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/24/2023] [Indexed: 04/29/2023]
Abstract
In the past decades the incidence of colorectal cancer (CRC) in people under the age of 50 years has increased, which is referred to as early-onset CRC or young-onset CRC (YO-CRC). YO-CRC is expected to account for 11% of colon cancers and 23% of rectal cancers by 2030. This trend is observed in different parts of the world and in both men and women. In 20% of patients with YO-CRC, a hereditary cancer syndrome is found as the underlying cause; however, in the majority of patients no genetic predisposition is present. Beginning in the 1950s, major changes in lifestyle such as antibiotic use, low physical activity and obesity have affected the gut microbiome and may be an important factor in YO-CRC development. Owing to a lack of screening, patients with YO-CRC are often diagnosed with advanced-stage disease. Long-term treatment-related complications should be taken into account in these younger patients, making the more traditional sequential approaches of drug therapy not always the most appropriate option. To better understand the underlying mechanism and define relationships between environmental factors and YO-CRC development, long-term prospective studies are needed with lifestyle data collected from childhood.
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Affiliation(s)
- Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, Netherlands.
| | - Ann G Zauber
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sapna Syngal
- Brigham and Women's Hospital, Boston, MA, USA
- Dana Farber Cancer Institute, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Martin J Blaser
- Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
| | - Joseph J Sung
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Y Nancy You
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center/Erasmus MC Cancer Institute, Rotterdam, Netherlands
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Ding J, Cao Y, Qi C, Zong Z. Dysregulated microRNAs participate in the crosstalk between colorectal cancer and atrial fibrillation. Hum Cell 2023:10.1007/s13577-023-00899-2. [PMID: 36964414 DOI: 10.1007/s13577-023-00899-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 03/16/2023] [Indexed: 03/26/2023]
Abstract
Colorectal cancer and atrial fibrillation share several common risk factors, and the incidence of the two diseases also exhibits a certain correlation. The above facts suggest a potential interaction mechanism between them, which has obtained increasing attention in the scientific community but remains to be further explored. Participating in diverse physiological and pathological processes, miRNAs exert important roles in both occurrence and growth of colorectal cancer and atrial fibrillation. To fill the gap in the understanding of the potential linkage between two diseases, the present study collected dysregulated miRNAs of colorectal cancer and atrial fibrillation from previous studies and then selected the miRNAs with the same change trends in both diseases. Finally, we reviewed the potential crosstalk of two diseases focusing on the roles of 6 dysregulated miRNAs, including 3 co-downregulated miRNAs (hsa-mir-126, hsa-mir-133a and hsa-mir-150) and 3 co-upregulated miRNAs (hsa-mir-106a, hsa-mir-155 and hsa-mir-21). The molecular mechanisms mediated by these miRNAs in colorectal cancer and atrial fibrillation were reviewed, and the possible crosstalk between the two diseases was discussed from the perspective of miRNAs. This study also provides potential common targets for preventive and curative measures against both colorectal cancer and atrial fibrillation.
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Affiliation(s)
- Jiatong Ding
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, 1 MinDe Road, Nanchang, 330006, China
- The Second Clinical Medicine School, Nanchang University, Nanchang, 330006, China
| | - Yuke Cao
- School of Ophthalmology and Optometry, Nanchang University, Nanchang, 330006, China
| | - Chaofan Qi
- The First Clinical Medicine School, Nanchang University, Nanchang, 330006, China
| | - Zhen Zong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, 1 MinDe Road, Nanchang, 330006, China.
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22
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Cavestro GM, Mannucci A, Balaguer F, Hampel H, Kupfer SS, Repici A, Sartore-Bianchi A, Seppälä TT, Valentini V, Boland CR, Brand RE, Buffart TE, Burke CA, Caccialanza R, Cannizzaro R, Cascinu S, Cercek A, Crosbie EJ, Danese S, Dekker E, Daca-Alvarez M, Deni F, Dominguez-Valentin M, Eng C, Goel A, Guillem JG, Houwen BBSL, Kahi C, Kalady MF, Kastrinos F, Kühn F, Laghi L, Latchford A, Liska D, Lynch P, Malesci A, Mauri G, Meldolesi E, Møller P, Monahan KJ, Möslein G, Murphy CC, Nass K, Ng K, Oliani C, Papaleo E, Patel SG, Puzzono M, Remo A, Ricciardiello L, Ripamonti CI, Siena S, Singh SK, Stadler ZK, Stanich PP, Syngal S, Turi S, Urso ED, Valle L, Vanni VS, Vilar E, Vitellaro M, You YQN, Yurgelun MB, Zuppardo RA, Stoffel EM. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines. Clin Gastroenterol Hepatol 2023; 21:581-603.e33. [PMID: 36549470 PMCID: PMC11207185 DOI: 10.1016/j.cgh.2022.12.006] [Citation(s) in RCA: 59] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/01/2022] [Accepted: 12/01/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.
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Affiliation(s)
- Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Alessandro Mannucci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesc Balaguer
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Heather Hampel
- Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California
| | - Sonia S Kupfer
- Department of Medicine, Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago Medicine, Chicago, Illinois
| | - Alessandro Repici
- Gastrointestinal Endoscopy Unit, Humanitas University, Humanitas Research Hospital, Rozzano, Italy
| | - Andrea Sartore-Bianchi
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Toni T Seppälä
- Faculty of Medicine and Medical Technology, University of Tampere and TAYS Cancer Centre, Arvo Ylpön katu, Tampere, Finland; Unit of Gastroenterological Surgery, Tampere University Hospital, Elämänaukio, Tampere, Finland; Applied Tumor Genomics Research Program and Department of Surgery, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Vincenzo Valentini
- Department of Radiology, Radiation Oncology and Hematology, Università Cattolica del Sacro Cuore di Roma, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
| | - Clement Richard Boland
- Department of Medicine, Division of Gastroenterology, University of California San Diego, San Diego, California
| | - Randall E Brand
- Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Tineke E Buffart
- Department of Medical Oncology. Amsterdam UMC, Location de Boelelaan, Amsterdam, The Netherlands
| | - Carol A Burke
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio
| | - Riccardo Caccialanza
- Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Renato Cannizzaro
- SOC Gastroenterologia Oncologica e Sperimentale Centro di Riferimento Oncologico di Aviano (CRO) IRCCS 33081, Aviano, Italy
| | - Stefano Cascinu
- Oncology Department, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Emma J Crosbie
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom; Division of Gynaecology, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Silvio Danese
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Maria Daca-Alvarez
- Department of Gastroenterology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Francesco Deni
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Mev Dominguez-Valentin
- Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
| | - Cathy Eng
- Department of Medicine, Division of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
| | - Ajay Goel
- Department of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, California
| | - Josè G Guillem
- Department of Surgery and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Britt B S L Houwen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Charles Kahi
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Matthew F Kalady
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Fay Kastrinos
- Division of Digestive and Liver Diseases, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center and the Vagelos College of Physicians and Surgeons, New York, New York
| | - Florian Kühn
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Luigi Laghi
- Department of Medicine and Surgery, University of Parma, Parma, and Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy
| | - Andrew Latchford
- Lynch Syndrome Clinic, Centre for Familial Intestinal Cancer, St Mark's Hospital, London North West University Healthcare NHS Trust, Harrow, United Kingdom
| | - David Liska
- Department of Colorectal Surgery and Edward J. DeBartolo Jr Family Center for Young-Onset Colorectal Cancer, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
| | - Patrick Lynch
- Department of Gastroenterology, M. D. Anderson Cancer Center, Houston, Texas
| | - Alberto Malesci
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gianluca Mauri
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy; IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy
| | - Elisa Meldolesi
- Department of Radiology, Radiation Oncology and Hematology, Università Cattolica del Sacro Cuore di Roma, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy
| | - Pål Møller
- Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
| | - Kevin J Monahan
- Lynch Syndrome Clinic, Centre for Familial Intestinal Cancer, St Mark's Hospital, London North West University Healthcare NHS Trust, Harrow, United Kingdom; Faculty of Medicine, Department of Surgery & Cancer, Imperial College, London, United Kingdom
| | - Gabriela Möslein
- Surgical Center for Hereditary Tumors, Ev. BETHESDA Khs. Duisburg, Academic Hospital University of Düsseldorf, Düsseldorf, Germany
| | - Caitlin C Murphy
- School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas
| | - Karlijn Nass
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
| | - Kimmie Ng
- Young-Onset Colorectal Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Cristina Oliani
- Medical Oncology, AULSS 5 Polesana, Santa Maria Della Misericordia Hospital, Rovigo, Italy
| | - Enrico Papaleo
- Centro Scienze della Natalità, Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Swati G Patel
- University of Colorado Anschutz Medical Center and Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado
| | - Marta Puzzono
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Remo
- Pathology Unit, Mater Salutis Hospital, ULSS9, Legnago, Verona, Italy
| | - Luigi Ricciardiello
- Department of Medical and Surgical Sciences, Universita degli Studi di Bologna, Bologna, Italy
| | - Carla Ida Ripamonti
- Department of Onco-Haematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
| | - Salvatore Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, and Department of Hematology Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Satish K Singh
- Department of Medicine, Section of Gastroenterology, VA Boston Healthcare System and Boston University, Boston, Massachusetts
| | - Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Peter P Stanich
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sapna Syngal
- Brigham and Women's Hospital, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Stefano Turi
- Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuele Damiano Urso
- Chirurgia Generale 3, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University Hospital of Padova, Padova, Italy
| | - Laura Valle
- Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell Program, Bellvitge Biomedical Research Center (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Madrid, Spain
| | - Valeria Stella Vanni
- Centro Scienze della Natalità, Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Eduardo Vilar
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Marco Vitellaro
- Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Yi-Qian Nancy You
- Department of Colon & Rectal Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Matthew B Yurgelun
- Brigham and Women's Hospital, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Raffaella Alessia Zuppardo
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elena M Stoffel
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan
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23
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Li H, Chen X, Hoffmeister M, Brenner H. Associations of smoking with early- and late-onset colorectal cancer. JNCI Cancer Spectr 2023; 7:7033469. [PMID: 36759940 PMCID: PMC9940696 DOI: 10.1093/jncics/pkad004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/21/2022] [Accepted: 01/06/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Smoking is an established risk factor of CRC risk, but evidence on its impact on early-onset CRC (EOCRC) risk is limited. We aimed to evaluate the association of smoking exposure with EOCRC and compare it with late-onset CRC (LOCRC). METHODS Smoking history and other known or suspected CRC risk factors were ascertained in detail in personal interviews among 6264 CRC patients and 6866 controls (frequency matched for age, sex, and county of residence) who were recruited in 2003-2020 in the DACHS study (Darmkrebs: Chancen der Verhütung durch Screening [German]; Colorectal Cancer: Chances for Prevention Through Screening [English]), a population-based case-control study from Germany. Associations of smoking with EOCRC (<55 years, 724 cases, 787 controls) and LOCRC (≥55years, 5540 cases, 6079 controls) were estimated using multiple logistic regression. RESULTS Smoking exposure was much higher among EOCRC cases than among controls, and strong associations of smoking were observed for both EOCRC and LOCR. Adjusted odds ratios for EOCRC and LOCRC were as follows: current smoking: 1.57 (95% confidence interval [CI] = 1.20 to 2.04, P < .001) and 1.46 (95% CI = 1.28 to 1.67, P < .001); former smoking: 1.39 (95% CI = 1.07 to 1.81, P = .01) and 1.24 (95% CI = 1.13 to 1.36, P < .001); per 10 pack-years: 1.15 (95% CI = 1.05 to 1.27, P < .001) and 1.05 (95% CI = 1.03 to 1.08, P < .001). These patterns were similar for colon and rectum cancer and for early- and late-stage CRC. CONCLUSION Smoking is a strong risk factor for both EOCRC and LOCRC.
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Affiliation(s)
- Hengjing Li
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany,Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany,Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Correspondence to: Hermann Brenner, MD, MPH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany (e-mail: )
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24
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Autoimmune and Metabolic Diseases and the Risk of Early-Onset Colorectal Cancer, a Nationwide Nested Case-Control Study. Cancers (Basel) 2023; 15:cancers15030688. [PMID: 36765646 PMCID: PMC9913656 DOI: 10.3390/cancers15030688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/19/2023] [Accepted: 01/19/2023] [Indexed: 01/24/2023] Open
Abstract
Incidence of early-onset (<50 years) colorectal cancer (EOCRC) is increasing in developed countries. The aim was to investigate autoimmune and metabolic conditions as risk factors for EOCRC. In a nationwide nested case-control study, we included all EOCRC cases in Sweden diagnosed during 2007-2016, together with controls, matched for birth year, sex, and county. Information on exposure of autoimmune or metabolic disease was collected from the National Patient Register and Prescribed Drugs Registry. Hazard ratios (HR) as measures of the association between EOCRC and the exposures were estimated using conditional logistic regression. In total, 2626 EOCRC patients and 15,756 controls were included. A history of metabolic disease nearly doubled the incidence hazard of EOCRC (HR 1.82, 95% CI 1.66-1.99). A sixfold increased incidence hazard of EOCRC (HR 5.98, 95% CI 4.78-7.48) was seen in those with inflammatory bowel disease (IBD), but the risk increment decreased in presence of concomitant metabolic disease (HR 3.65, 95% CI 2.57-5.19). Non-IBD autoimmune disease was not statistically significantly associated with EOCRC. IBD and metabolic disease are risk factors for EOCRC and should be considered in screening guidelines.
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25
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Hua H, Jiang Q, Sun P, Xu X. Risk factors for early-onset colorectal cancer: systematic review and meta-analysis. Front Oncol 2023; 13:1132306. [PMID: 37213277 PMCID: PMC10196487 DOI: 10.3389/fonc.2023.1132306] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 04/18/2023] [Indexed: 05/23/2023] Open
Abstract
Background The incidence of early-onset colorectal cancer (EOCRC), which means colorectal cancer diagnosed in patients under 50 years, has been increasing around the world. However, the etiology remains unclear. This study aims to identify risk factors for EOCRC. Methods This systematic review was conducted in PubMed, Embase, Scopus, and Cochrane Library databases from inception to November 25, 2022. We examined risk factors for EOCRC, including demographic factors, chronic conditions, and lifestyle behaviors or environmental factors. Random-effects/fixed-effects meta-analysis was adopted to combine effect estimates from published data. Study quality was evaluated with the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed Revman5.3. Studies not suitable for the meta-analysis were analyzed by a systematic review. Results A total of 36 studies were identified for this review, and 30 studies were included in the meta-analysis. Significant risk factors for EOCRC included male (OR=1.20; 95% CI, 1.08-1.33), Caucasian (OR=1.44; 95% CI, 1.15-1.80), a family history of CRC (OR=5.90; 95% CI, 3.67-9.48), inflammatory bowel disease (OR=4.43; 95% CI, 4.05-4.84), obesity (OR=1.52; 95%CI, 1.20-1.91), overweight (OR=1.18; 95% CI, 1.12-1.25), triglycerides (OR=1.12; 95% CI, 1, 08-1.18), hypertension (OR=1.16; 95% CI, 1.12-1.21), metabolic syndrome (OR=1.29; 95% CI, 1.15-1.45), smoking (OR=1.44; 95% CI, 1.10-1.88), alcohol consumption (OR=1.41; 95% CI, 1.22-1.62), a sedentary lifestyle (OR=1.24; 95% CI, 1.05-1.46), red meat (OR=1.10; 95% CI, 1.04-1.16), processed meat (OR=1.53; 95% CI, 1.13-2.06), Western dietary patterns (OR=1.43; 95% CI, 1.18-1.73) and sugar-sweetened beverages (OR=1.55; 95% CI, 1.23-1.95). However, no statistical differences were found for hyperlipidemia and hyperglycemia. Vitamin D may be a protective factor (OR=0.72; 95% CI, 0.56-0.92). There was considerable heterogeneity among studies (I2>60%). Conclusions The study provides an overview of the etiology and risk factors of EOCRC. Current evidence can provide baseline data for risk prediction models specific to EOCRC and risk-tailored screening strategies.
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Ugai T, Sasamoto N, Lee HY, Ando M, Song M, Tamimi RM, Kawachi I, Campbell PT, Giovannucci EL, Weiderpass E, Rebbeck TR, Ogino S. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022; 19:656-673. [PMID: 36068272 PMCID: PMC9509459 DOI: 10.1038/s41571-022-00672-8] [Citation(s) in RCA: 260] [Impact Index Per Article: 86.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2022] [Indexed: 02/07/2023]
Abstract
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased use of screening programmes has contributed to this phenomenon to a certain extent, although a genuine increase in the incidence of early-onset forms of several cancer types also seems to have emerged. Evidence suggests an aetiological role of risk factor exposures in early life and young adulthood. Since the mid-20th century, substantial multigenerational changes in the exposome have occurred (including changes in diet, lifestyle, obesity, environment and the microbiome, all of which might interact with genomic and/or genetic susceptibilities). However, the effects of individual exposures remain largely unknown. To study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data collection technologies. Raising awareness among both the public and health-care professionals will also be critical. In this Review, we describe changes in the incidence of early-onset cancers globally and suggest measures that are likely to reduce the burden of cancers and other chronic non-communicable diseases.
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Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA
| | - Hwa-Young Lee
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Institute of Convergence Science, Convergence Science Academy, Yonsei University, Seoul, Republic of Korea
| | - Mariko Ando
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
| | - Ichiro Kawachi
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Timothy R Rebbeck
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA
- Zhu Family Center for Global Cancer Prevention, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
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Gu WJ, Pei JP, Lyu J, Akimoto N, Haruki K, Ogino S, Zhang CD. The Burden of Early-Onset Colorectal Cancer and Its Risk Factors from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Cancers (Basel) 2022; 14:3502. [PMID: 35884567 PMCID: PMC9323588 DOI: 10.3390/cancers14143502] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/11/2022] [Accepted: 07/13/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The incidence of early-onset colorectal cancer (CRC) diagnosed before age 50 has been increasing over the past decades. Hence, we examined the global, regional, and national burden of early-onset CRC and its risk factors from 1990 to 2019. METHODS Using data from the Global Burden of Disease (GBD) Study 2019, we reported the incidence, deaths, and disability-adjusted life-years (DALYs) attributable to the risk factors of early-onset CRC. All estimates were reported with 95% uncertainty intervals (UIs). RESULTS The global numbers of early-onset CRC for incidence, deaths, and DALYs in 2019 were 225,736 (95% UI, 207,658 to 246,756), 86,545 (80,162 to 93,431), and 4,259,922 (3,942,849 to 4,590,979), respectively. Despite large variations at the regional and national levels, the global incidence rate, death rate, and DALY rate increased from 1990 to 2019. Diets low in milk, diets low in calcium, and alcohol use were the leading risk factors in 2019. From 1990 to 2019, a high body mass index and high fasting plasma glucose ranked remarkably higher among males and females, while smoking and diets low in fiber ranked lower among both sexes, with a more profound change among females. CONCLUSIONS Despite large variations in regional and national levels, the global incidence rate, death rate, and DALY rate increased during the past three decades. These findings may provide policymakers with an accurate quantification of the burden of early-onset CRC and targeted identification of those most at risk to mitigate the burden of early-onset CRC.
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Affiliation(s)
- Wan-Jie Gu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; (W.-J.G.); (J.L.)
| | - Jun-Peng Pei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, China;
| | - Jun Lyu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; (W.-J.G.); (J.L.)
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (N.A.); (K.H.); (S.O.)
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (N.A.); (K.H.); (S.O.)
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (N.A.); (K.H.); (S.O.)
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA 02115, USA
| | - Chun-Dong Zhang
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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28
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Chen X, Li H, Guo F, Hoffmeister M, Brenner H. Alcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk. EClinicalMedicine 2022; 49:101460. [PMID: 35747198 PMCID: PMC9126769 DOI: 10.1016/j.eclinm.2022.101460] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/29/2022] [Accepted: 05/02/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Evidence is lacking on the impact of alcohol consumption on colorectal cancer (CRC) risk (overall and by age at diagnosis) by polygenic risk score (PRS) levels, and it is unclear how the magnitude of CRC risk associated with alcohol consumption compares to the magnitude of genetically determined risk. METHODS Multiple logistic regression was used to assess the association between alcohol consumption and colorectal cancer (CRC) across PRS levels based on 140 CRC-related loci among 5104 CRC cases and 4131 controls from a large population-based case-control study. We compared the effects for alcohol consumption and PRS on CRC risk using the "Genetic Risk Equivalent (GRE)" for effective risk communication. Specific analyses were conducted for early-onset CRC (EOCRC, <55 years) and late-onset CRC (LOCRC, ≥55 years). FINDINGS High alcohol consumption, and to a lower extent, also alcohol abstinence were associated with increased CRC risk. Compared to low alcohol consumption (0·1-<25 g/d), lifetime average alcohol consumption ≥25 g/d was more strongly associated with EOCRC [odds ratio (OR) 1·8, 95% confidence interval (CI) 1·2-2·8] than with LOCRC risk (OR 1·3, 95% CI 1·1-1·4) (P-value for interaction with age =0·011). Interactions between alcohol consumption and PRS did not reach statistical significance for either EOCRC or LOCRC risk. The estimated impact of high lifetime alcohol consumption on EOCRC was equivalent to the effect of having 47 percentiles higher PRS (GRE 47, 95% CI 12-82), stronger than the impact on LOCRC (GRE 18, 95% CI 8-29). INTERPRETATION Excessive alcohol use was strongly associated with EOCRC risk, independent of PRS levels. Abstaining from heavy drinking could reduce risk for CRC, in particular for EOCRC to an extent that would be equivalent to having a much lower genetically determined risk. FUNDING The first author (X.C.) was supported by the Guangzhou Elite Project (GEP). The DACHS study was supported by grants from the German Research Council (BR 1704/6-1, BR1704/6-3, BR 1704/6-4, BR 1704/6-6, CH 117/1-1, BR 1704/17-1, HO 5117/2-1) and the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01GL1712).
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Key Words
- Alcohol consumption
- CI, confidence interval
- CRC, colorectal cancer
- DACHS, Darmkrebs: Chancen der Verhütung durch Screening
- EOCRC, early-onset colorectal cancer
- Early-onset colorectal cancer
- GRE, genetic risk equivalent
- GWAS, genome-wide association study
- Genetic risk equivalentt
- LOCRC, late-onset colorectal cancer
- Late-onset colorectal cancer
- NSAID, non-steroidal anti-inflammatory drug
- OR, odds ratio
- PRS, polygenic risk score
- Polygenic risk score
- SNP, single nucleotide polymorphisms
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Affiliation(s)
- Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Hengjing Li
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Feng Guo
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg, Germany
- Corresponding author at: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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29
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Raimondi A, Randon G, Prisciandaro M, Pagani F, Lonardi S, Antoniotti C, Bozzarelli S, Sartore-Bianchi A, Tampellini M, Fanchini L, Murialdo R, Clavarezza M, Zaniboni A, Berenato R, Ratti M, Petrelli F, Antonuzzo L, Giordano M, Rossi A, Di Bartolomeo M, Di Maio M, Pietrantonio F, Morano F. Early onset metastatic colorectal cancer in patients receiving panitumumab-based upfront strategy: Overall and sex-specific outcomes in the Valentino trial. Int J Cancer 2022; 151:1760-1769. [PMID: 35678328 DOI: 10.1002/ijc.34156] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 11/12/2022]
Abstract
Anti-EGFRs plus doublet chemotherapy is considered the optimal upfront option for RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). Early-onset (EO) mCRC has an increasing incidence and its prognostic/predictive role and management is debatable. We performed a post hoc analysis of Valentino study, that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after FOLFOX/panitumumab induction. We assessed the safety and efficacy outcomes in patients stratified for age (<50/≥50 years old). We assessed progression-free survival (PFS), overall survival (OS), response rate (ORR), rate of treatment-related and panitumumab-related adverse events (AEs) and quality of life (QoL). In 229 patients enrolled, 35 (15%) had EO mCRC, with a higher rate of female sex (P = .020) and lower rate of primary tumor resection (P = .001). Median PFS and OS were 10.9 vs 10.8 months (P = .593) and 28.1 vs 27.5 months (P = .865) in patients <50 and ≥50 years old, respectively, with no significant impact of maintenance arm. ORR and disease control rate were 74% vs 65% (P = .337) and 97% vs 81% (P = .013) in patients <50 or ≥50 years old. In younger patients, a trend for increased chemotherapy-related AEs (peculiarly anemia) was shown, while significantly decreased EGFR-related hypomagnesemia and increased skin rash were reported. No significant differences in treatment intensity or QoL were observed. In patients with EO mCRC and RAS wild-type status, we found no differences in terms of survival outcomes based on age when selecting maintenance strategies. Management of treatment-related AEs should consider the differential toxicity profile of age and sex.
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Affiliation(s)
- Alessandra Raimondi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Giovanni Randon
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Michele Prisciandaro
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,Oncology and Hemato-oncology Department, University of Milan, Milan, Italy
| | - Filippo Pagani
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Sara Lonardi
- Department of Oncology, Veneto Institute of Oncology IRCCS, Padua, Italy
| | - Carlotta Antoniotti
- Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Silvia Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Andrea Sartore-Bianchi
- Oncology and Hemato-oncology Department, University of Milan, Milan, Italy.,Division of Oncology, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marco Tampellini
- Department of Oncology, AOU San Luigi di Orbassano, University of Torino, Orbassano, Italy
| | - Laura Fanchini
- SSD ColoRectal Cancer Unit-Dipartimento di Oncologia, AOU Città della Salute e della Scienza di Torino, Torino, Italy
| | - Roberto Murialdo
- Department of Internal Medicine, University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy
| | - Matteo Clavarezza
- Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy
| | | | | | | | - Fausto Petrelli
- Medical Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio, Italy
| | - Lorenzo Antonuzzo
- Clinical Oncology Unit, AOU Careggi, Florence, Italy.,Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Monica Giordano
- Medical Oncology Unit, Azienda Socio Sanitaria Territoriale Lariana, Como, Italy
| | - Alessandro Rossi
- Department of Clinical and Molecular Medicine, Oncology Unit, "La Sapienza" University of Rome, Azienda Ospedaliera Sant'Andrea, Rome, Italy
| | - Maria Di Bartolomeo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Massimo Di Maio
- Department of Oncology, University of Turin, Division of Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy
| | - Filippo Pietrantonio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federica Morano
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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30
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O'Sullivan DE, Sutherland RL, Town S, Chow K, Fan J, Forbes N, Heitman SJ, Hilsden RJ, Brenner DR. Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:1229-1240.e5. [PMID: 33524598 DOI: 10.1016/j.cgh.2021.01.037] [Citation(s) in RCA: 176] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/18/2021] [Accepted: 01/24/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Despite the widespread increase in the incidence of early-onset colorectal cancer (EoCRC), the reasons for this increase remain unclear. The objective of this study was to determine risk factors for the development of EoCRC. METHODS We conducted a systematic literature review and meta-analysis of studies examining non-genetic risk factors for EoCRC, including demographic factors, comorbidities, and lifestyle factors. Random effects meta-analyses were conducted for risk factors that were examined in at least three studies. Heterogeneity was investigated using the Q-test and I2 statistic. RESULTS From 3304 initial citations, 20 studies were included in this review. Significant risk factors for EoCRC included CRC history in a first-degree relative (RR 4.21, 95% CI 2.61-6.79), hyperlipidemia (RR 1.62, 95% CI 1.22-2.13), obesity (RR 1.54, 95% CI 1.01-2.35), and alcohol consumption (high vs. non-drinkers) (RR 1.71, 95% CI 1.62-1.80). While smoking was suggestive as a risk factor, the association was not statistically significant (RR 1.35, 95% CI 0.81-2.25). With the exception of alcohol consumption, there was considerable heterogeneity among studies (I2 > 60%). Other potential risk factors included hypertension, metabolic syndrome, ulcerative colitis, chronic kidney disease, dietary factors, sedentary behaviour, and occupational exposure to organic dusts, but these were only examined in one or two studies. CONCLUSIONS The results of this study advance the understanding of the etiology of EoCRC. High-quality studies conducted on generalizable populations and that comprehensively examine risk factors for EoCRC are required to inform primary and secondary prevention strategies.
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Affiliation(s)
- Dylan E O'Sullivan
- Department of Community Health Sciences, University of Calgary, Calgary, AB; Department of Oncology, University of Calgary, Calgary, AB; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB
| | - R Liam Sutherland
- Department of Community Health Sciences, University of Calgary, Calgary, AB; Department of Oncology, University of Calgary, Calgary, AB; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB
| | - Susanna Town
- Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB
| | - Kristian Chow
- Department of Community Health Sciences, University of Calgary, Calgary, AB
| | - Jeremy Fan
- Department of Community Health Sciences, University of Calgary, Calgary, AB
| | - Nauzer Forbes
- Department of Community Health Sciences, University of Calgary, Calgary, AB; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Steven J Heitman
- Department of Community Health Sciences, University of Calgary, Calgary, AB; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Robert J Hilsden
- Department of Community Health Sciences, University of Calgary, Calgary, AB; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Darren R Brenner
- Department of Community Health Sciences, University of Calgary, Calgary, AB; Department of Oncology, University of Calgary, Calgary, AB; Forzani & MacPhail Colon Cancer Screening Centre, Alberta Health Services, Calgary, AB.
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31
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Abstract
Contrary to decreasing incidence rate of colorectal cancer (CRC) in older adults, incidence rates have nearly doubled in younger adults (age <50 years) in the United States since the early 1990s. A similar increase has been observed across the globe. Despite overall population trends in aging, about 15% of CRCs will be diagnosed in younger adults by 2030. The mechanisms and factors contributing to early-onset CRC (EOCRC) remain puzzling, especially because most young adults diagnosed with CRC have no known risk factors or predisposing conditions, such as family history of CRC or polyps or a hereditary syndrome (eg, Lynch syndrome, polyposis). In this up-to-date review, we discuss the current knowledge of EOCRC, including epidemiology, risk factors, clinical and molecular features, treatment and survival, and recognition and screening strategies.
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Affiliation(s)
- Pooja Dharwadkar
- Division of Gastroenterology, Department of Medicine, University of California San Francisco, Zuckerberg San Francisco General, Building 5, 3rd Floor, Suite 3D, 1001 Potrero Avenue, San Francisco, CA 94110, USA
| | - Timothy A Zaki
- Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
| | - Caitlin C Murphy
- UTHealth School of Public Health, Suite 2618, 7000 Fannin Street, Houston, TX 77030, USA.
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32
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Hypoxia as a Modulator of Inflammation and Immune Response in Cancer. Cancers (Basel) 2022; 14:cancers14092291. [PMID: 35565420 PMCID: PMC9099524 DOI: 10.3390/cancers14092291] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/25/2022] [Accepted: 04/25/2022] [Indexed: 02/01/2023] Open
Abstract
A clear association between hypoxia and cancer has heretofore been established; however, it has not been completely developed. In this sense, the understanding of the tumoral microenvironment is critical to dissect the complexity of cancer, including the reduction in oxygen distribution inside the tumoral mass, defined as tumoral hypoxia. Moreover, hypoxia not only influences the tumoral cells but also the surrounding cells, including those related to the inflammatory processes. In this review, we analyze the participation of HIF, NF-κB, and STAT signaling pathways as the main components that interconnect hypoxia and immune response and how they modulate tumoral growth. In addition, we closely examine the participation of the immune cells and how they are affected by hypoxia, the effects of the progression of cancer, and some innovative applications that take advantage of this knowledge, to suggest potential therapies. Therefore, we contribute to the understanding of the complexity of cancer to propose innovative therapeutic strategies in the future.
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33
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Cao L, Dong G, Li H. CircRNA circ-ATAD1 suppresses miR-618 maturation to participate in colorectal cancer. BMC Gastroenterol 2022; 22:215. [PMID: 35505304 PMCID: PMC9063078 DOI: 10.1186/s12876-022-02183-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 02/24/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND CircRNA circ-ATAD1 has been characterized as an oncogenic circRNA in gastric cancer, while its role in colorectal cancer (CRC) is unknown. This study was carried out to explore the role of circ-ATAD1 in CRC. METHODS Paired CRC and adjacent non-tumor tissue samples collected from 64 CRC patients were subjected to RNA extractions and RT-qPCRs to analyze the expression of circ-ATAD1, premature miR-618, and mature miR-618 in CRC. The effects of circ-ATAD1 overexpression on miR-618 maturation were analyzed by transfecting circ-ATAD1 expression vector into CRC cells, followed by determining the expression of premature miR-618 and mature miR-618 using RT-qPCR. The subcellular location of circ-ATAD1 was analyzed by nuclear fractionation assay, and the interaction between circ-ATAD1 and premature miR-618 was analyzed by RNA pull-down assay. The roles of circ-ATAD1, premature miR-618, and mature miR-618 in regulating CRC cell proliferation were explored by CCK-8 assay. RESULTS Circ-ATAD1 was upregulated in CRC and predicted poor survival. In addition, circ-ATAD1 was inversely correlated with mature miR-618 but not premature miR-618. In CRC cells, circ-ATAD1 overexpression decreased the level of mature miR-618 but not premature miR-618. Circ-ATAD1 was detected in both the nucleus and cytoplasm. A direct interaction between circ-ATAD1 and miR-618 was observed. Moreover, circ-ATAD1 overexpression reduced the inhibitory effects of miR-618 overexpression on cell proliferation. CONCLUSION Circ-ATAD1 is overexpressed in CRC and may suppress miR-618 maturation to participate in CRC.
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Affiliation(s)
- Li Cao
- Department of Hepatology Surgery, Department of Liver Medicine, Fifth Medical Center, General Hospital of PLA, Beijing, 100039, People's Republic of China
| | - Guanglong Dong
- Department of General Surgery, The General Hospital of People's Liberation Army, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
| | - Huan Li
- Military Science Press, Beijing, 100091, People's Republic of China
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34
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Syed A, Seoud T, Carleton NM, Thakkar S, Kiran RP, Shen B. Association Between Portal Vein Thrombosis and Pouchitis in Patients with Ulcerative Colitis. Dig Dis Sci 2022; 67:1303-1310. [PMID: 33948758 DOI: 10.1007/s10620-021-06969-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 03/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Pouchitis is the most common long-term complication in patients requiring colectomy ileal pouch-anal anastomosis with medically refractory ulcerative colitis or colitis-associated neoplasia. A previous small case series suggests associated between portal vein thrombosis (PVT) and ischemic pouchitis. AIM To evaluate the association between PVT and other demographic and clinical factors and pouchitis. METHODS We used Explorys Inc., a population-based database, to search medical records between 1999 and 2020 with SNOMED-CT code criteria for "construction of pouch" and "ileal pouchitis." Patients with pouchitis were compared to those with previous pouch construction without pouchitis. Factors associated with pouchitis identified with univariable analysis were introduced into a multivariable model. A post hoc analysis further stratified demographical findings of the association between PVT and pouchitis. RESULTS We identified 7900 patients with ileal pouchitis (7.5%) and 97,510 with pouch construction without pouchitis. In multivariate binary logistic regression, adjusted odds ratio (aOR) for the risk of pouchitis in patients with PVT was 10.78 (95% confidence interval [CI] 7.04-16.49, P < 0.001). Other significant factors associated with pouchitis included male gender (aOR 1.11, 95% CI 1.02-1.21, P = 0.018), deep vein thrombosis (aOR 1.46, 95% CI 1.23-1.72, P < 0.001), and the use of non-steroidal anti-inflammatory drugs (aOR 1.37, 95% CI 1.28-1.45, P < 0.001). Smoking was a protective factor (aOR 0.30, 95% CI 0.33-0.36, P < 0.001). Further sub-analysis showed a higher prevalence of younger patients with PVT and pouchitis. CONCLUSIONS We report PVT as an independent risk factor associated with pouchitis. Our findings support that PVT is a potentially manageable perioperative complication, and intervention may reduce the risk of pouchitis.
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Affiliation(s)
- Aslam Syed
- Division of Gastroenterology, Allegheny Health Network, Pittsburgh, PA, USA.,Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA
| | - Talal Seoud
- Division of Gastroenterology and Hepatology, Stony Brook University Hospital, Long Island, NY, USA
| | - Neil M Carleton
- Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Shyam Thakkar
- Adjunct Faculty, Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA
| | - Ravi P Kiran
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/New York Presbyterian Hospital, Herbert Irving Pavilion-Rm 843, 161 Fort Washington Ave, New York, NY, 10032, USA
| | - Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/New York Presbyterian Hospital, Herbert Irving Pavilion-Rm 843, 161 Fort Washington Ave, New York, NY, 10032, USA.
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35
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Gu J, Li Y, Yu J, Hu M, Ji Y, Li L, Hu C, Wei G, Huo J. A risk scoring system to predict the individual incidence of early-onset colorectal cancer. BMC Cancer 2022; 22:122. [PMID: 35093005 PMCID: PMC8801093 DOI: 10.1186/s12885-022-09238-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 01/20/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND The incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate and further studies are needed to identify risk factors and to develop prevention strategies. METHODS Risk factors significantly associated with EOCRC were identified using meta-analysis. An individual risk appraisal model was constructed using the Rothman-Keller model. Next, a group of random data sets was generated using the binomial distribution function method, to determine nodes of risk assessment levels and to identify low, medium, and high risk populations. RESULTS A total of 32,843 EOCRC patients were identified in this study, and nine significant risk factors were identified using meta-analysis, including male sex, Caucasian ethnicity, sedentary lifestyle, inflammatory bowel disease, and high intake of red meat and processed meat. After simulating the risk assessment data of 10,000 subjects, scores of 0 to 0.0018, 0.0018 to 0.0036, and 0.0036 or more were respectively considered as low-, moderate-, and high-risk populations for the EOCRC population based on risk trends from the Rothman-Keller model. CONCLUSION This model can be used for screening of young adults to predict high risk of EOCRC and will contribute to the primary prevention strategies and the reduction of risk of developing EOCRC.
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Affiliation(s)
- Jialin Gu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China
| | - Yan Li
- Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China
| | - Jialin Yu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Miao Hu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China
| | - Yi Ji
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Lingchang Li
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Canhong Hu
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China
| | - Guoli Wei
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China.
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China.
- Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, Jiangsu, China.
- Yangzhou University Medical College, Yangzhou, 225000, Jiangsu, China.
| | - Jiege Huo
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, P.R. China.
- Department of Oncology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China.
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Ahmad Kendong SM, Raja Ali RA, Nawawi KNM, Ahmad HF, Mokhtar NM. Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer. Front Cell Infect Microbiol 2021; 11:744606. [PMID: 34966694 PMCID: PMC8710575 DOI: 10.3389/fcimb.2021.744606] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.
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Affiliation(s)
- Siti Maryam Ahmad Kendong
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.,Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia
| | - Raja Affendi Raja Ali
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.,GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Khairul Najmi Muhammad Nawawi
- Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.,GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Hajar Fauzan Ahmad
- Department of Industrial Biotechnology, Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Gambang, Malaysia.,Center for Research in Advanced Tropical Bioscience, Universiti Malaysia Pahang, Gambang, Malaysia
| | - Norfilza Mohd Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.,GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review. Cancers (Basel) 2021; 13:cancers13235933. [PMID: 34885046 PMCID: PMC8657307 DOI: 10.3390/cancers13235933] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/16/2021] [Accepted: 11/24/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary This systematic review sifted through the exogenous dietary and lifestyle risk factors associated with early-onset colorectal cancer, going through the putative involvement of these exogenous risk factors in epigenetic and microbiota modifications. Given the burden of early-onset colorectal cancer and its globally increasing trend with scant literature on its pathogenesis, we believe it would be of benefit to highlight the importance of further systematic and large studies. Indeed, dietary and lifestyle modification could complement colorectal screening for early-onset colorectal cancer prevention. Abstract The incidence of early-onset colorectal cancer, defined as colorectal cancer occurring in young adults under the age of 50, is increasing globally. Knowledge of the etiological factors in young adults is far from complete. Questionable eoCRCs’ exogenous factors are represented by processed meat, sugary drinks, alcohol, Western dietary pattern, overweight and obesity, physical inactivity, and smoking, though with heterogeneous results. Therefore, we performed a systematic review to summarize the current evidence on the role of diet and lifestyle as eoCRC risk factors. We systematically searched PubMed, Scopus, and EMBASE up to July 2021, for original studies evaluating diet, alcohol, physical activity, BMI, and smoking in eoCRC and included twenty-six studies. Indeed, the exogenous factors could represent modifiable key factors, whose recognition could establish areas of future interventions through public health strategies for eoCRC primary prevention. Additionally, we discussed the role of additional non-modifiable risk factors, and of epigenetic regulation and microbiota as mediators of the eoCRC triggered by diet and lifestyle.
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Makmun D, Simadibrata M, Abdullah M, Syam AF, Shatri H, Fauzi A, Renaldi K, Maulahela H, Utari AP, Pribadi RR, Muzellina VN, Nursyirwan SA. Colorectal cancer patients in a tertiary hospital in Indonesia: Prevalence of the younger population and associated factors. World J Clin Cases 2021; 9:9804-9814. [PMID: 34877319 PMCID: PMC8610908 DOI: 10.12998/wjcc.v9.i32.9804] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/15/2021] [Accepted: 09/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An increasing trend in colorectal cancer (CRC) occurring at younger ages has been observed worldwide, even though incidence is declining in the general population. Most currently available guidelines still recommend CRC screening for older populations, despite an alarming rise in early-onset CRC incidence. Risk stratification is necessary to further determine the population most at risk for early-onset CRC. However, epidemiological data on related clinical characteristics and potential risk factors, especially in developing countries, have not been widely reported. AIM To investigate the prevalence, demographics, clinicopathologic features, and associated factors of young-onset CRC patients in a tertiary hospital in Indonesia. METHODS Patients undergoing colonoscopy examination between 2008 and 2019, yielding a diagnosis of CRC were identified from medical records. The subjects were classified into two groups according to their age at diagnosis, namely early-onset (18-49 years old) and late-onset (≥ 50-years-old). Demographic data, characteristics, and risk factors of both onset age groups were evaluated using the chi-square and Fisher's exact test. RESULTS Among 495 CRC patients confirmed by histopathology, 205 (41.4%) were classified as early-onset and 290 (58.6%) as late-onset. Most subjects in the early-onset CRC group were male (53.7%), with 89.8% displaying adenocarcinoma histopathology. A majority (78%) of the early-onset CRC patients had left-sided tumors, with the rectum (41%) and rectosigmoid (17.6%) being the most common sites. Abdominal pain was the most frequent symptom in the early-onset CRC patients (55.6%), which was significantly higher than that in the late-onset CRC patients (43.8%, P < 0.05). Early-onset CRC cases were more likely to be underweight (34.6% vs 20.0%, P < 0.001) compared to late-onset CRC cases. The proportion of subjects with suspected hereditary nonpolyposis colorectal cancer (HNPCC) was also higher in the early-onset CRC group than in the late-onset age group (9.3% vs 4.1%, P < 0.05). However, no difference was observed in the parental or family histories of CRC cases. CONCLUSION Early-onset CRC patients were more likely to have abdominal pain, underweight status, and HNPCC suspicion than late-onset CRC patients.
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Affiliation(s)
- Dadang Makmun
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Marcellus Simadibrata
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Ari F Syam
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Hamzah Shatri
- Clinical Epidemiology Unit, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Achmad Fauzi
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Kaka Renaldi
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Hasan Maulahela
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Amanda P Utari
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Rabbinu R Pribadi
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Virly N Muzellina
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
| | - Saskia A Nursyirwan
- Division of Gastroenterology, Pancreatobiliary & Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
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Li H, Boakye D, Chen X, Hoffmeister M, Brenner H. Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis. Am J Gastroenterol 2021; 116:2173-2183. [PMID: 34309586 PMCID: PMC8560162 DOI: 10.14309/ajg.0000000000001393] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 06/10/2021] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Incidence of colorectal cancer (CRC) in young adults has been increasing in recent decades in many countries for still widely unclear reasons. Suspected candidates include increasing prevalence of overweight and obesity, but specific evidence on their role for early-onset CRC (EOCRC) is sparse. We conducted a systematic review and meta-analysis to summarize available evidence on the association of body mass index (BMI) with EOCRC. METHODS We systematically searched PubMed, EMBASE, and Web of Science up to February 2021 for studies that evaluated the association of BMI (before diagnosis but not near diagnosis) with CRC risk and reported specific results for EOCRC. Results from studies with similar BMI groupings were summarized in meta-analyses using random-effects models. RESULTS Twelve studies were eligible and included. Results of 6 studies were pooled in meta-analyses, which yielded a higher risk of EOCRC for overweight and obesity (BMI ≥25 kg/m2) compared with normal weight (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.68). An increasing risk with increasing BMI was observed, with much higher risk for obesity (OR 1.88, 95% CI 1.40-2.54) than for overweight (OR 1.32, 95% CI 1.19-1.47). DISCUSSION Obesity is a strong risk factor for EOCRC, and its increasing prevalence in younger generations is likely to substantially contribute to the increase in EOCRC. Efforts to limit the obesity epidemic in adolescents and younger adults may be crucial for reducing CRC incidence in future generations of adults.
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Affiliation(s)
- Hengjing Li
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Daniel Boakye
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
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40
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Himbert C, Figueiredo JC, Shibata D, Ose J, Lin T, Huang LC, Peoples AR, Scaife CL, Pickron B, Lambert L, Cohan JN, Bronner M, Felder S, Sanchez J, Dessureault S, Coppola D, Hoffman DM, Nasseri YF, Decker RW, Zaghiyan K, Murrell ZA, Hendifar A, Gong J, Firoozmand E, Gangi A, Moore BA, Cologne KG, El-Masry MS, Hinkle N, Monroe J, Mutch M, Bernadt C, Chatterjee D, Sinanan M, Cohen SA, Wallin U, Grady WM, Lampe PD, Reddi D, Krane M, Fichera A, Moonka R, Herpel E, Schirmacher P, Kloor M, von Knebel-Doeberitz M, Nattenmueller J, Kauczor HU, Swanson E, Jedrzkiewicz J, Schmit SL, Gigic B, Ulrich AB, Toriola AT, Siegel EM, Li CI, Ulrich CM, Hardikar S. Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset. Cancers (Basel) 2021; 13:cancers13153817. [PMID: 34359718 PMCID: PMC8345133 DOI: 10.3390/cancers13153817] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 01/13/2023] Open
Abstract
Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (<50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III-IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82-3.83) and 2.00 (1.43-2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21-1.98) and 0.56 (0.41-0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.
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Affiliation(s)
- Caroline Himbert
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Jane C. Figueiredo
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - David Shibata
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 37996, USA; (D.S.); (N.H.); (J.M.)
| | - Jennifer Ose
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Tengda Lin
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Lyen C. Huang
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Anita R. Peoples
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Courtney L. Scaife
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
| | - Bartley Pickron
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
| | - Laura Lambert
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
| | - Jessica N. Cohan
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
| | - Mary Bronner
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
| | - Seth Felder
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; (S.F.); (J.S.); (S.D.); (D.C.); (S.L.S.); (E.M.S.)
| | - Julian Sanchez
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; (S.F.); (J.S.); (S.D.); (D.C.); (S.L.S.); (E.M.S.)
| | - Sophie Dessureault
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; (S.F.); (J.S.); (S.D.); (D.C.); (S.L.S.); (E.M.S.)
| | - Domenico Coppola
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; (S.F.); (J.S.); (S.D.); (D.C.); (S.L.S.); (E.M.S.)
| | - David M. Hoffman
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Yosef F. Nasseri
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Robert W. Decker
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Karen Zaghiyan
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Zuri A. Murrell
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Andrew Hendifar
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Jun Gong
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Eiman Firoozmand
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Alexandra Gangi
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Beth A. Moore
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Kyle G. Cologne
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Maryliza S. El-Masry
- Cedars-Sinai Center, Los Angeles, CA 90048, USA; (J.C.F.); (D.M.H.); (Y.F.N.); (R.W.D.); (K.Z.); (Z.A.M.); (A.H.); (J.G.); (E.F.); (A.G.); (B.A.M.); (K.G.C.); (M.S.E.-M.)
| | - Nathan Hinkle
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 37996, USA; (D.S.); (N.H.); (J.M.)
| | - Justin Monroe
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 37996, USA; (D.S.); (N.H.); (J.M.)
| | - Matthew Mutch
- Department of Surgery, Washington University St. Louis, St. Louis, MO 63130, USA; (M.M.); (C.B.); (D.C.); (A.T.T.)
| | - Cory Bernadt
- Department of Surgery, Washington University St. Louis, St. Louis, MO 63130, USA; (M.M.); (C.B.); (D.C.); (A.T.T.)
| | - Deyali Chatterjee
- Department of Surgery, Washington University St. Louis, St. Louis, MO 63130, USA; (M.M.); (C.B.); (D.C.); (A.T.T.)
| | - Mika Sinanan
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
| | - Stacey A. Cohen
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
| | - Ulrike Wallin
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
| | - William M. Grady
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
| | - Paul D. Lampe
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
| | - Deepti Reddi
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
| | - Mukta Krane
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA
| | | | - Ravi Moonka
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
| | - Esther Herpel
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Peter Schirmacher
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Matthias Kloor
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Magnus von Knebel-Doeberitz
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Johanna Nattenmueller
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Hans-Ulrich Kauczor
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Eric Swanson
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
| | - Jolanta Jedrzkiewicz
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Stephanie L. Schmit
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; (S.F.); (J.S.); (S.D.); (D.C.); (S.L.S.); (E.M.S.)
| | - Biljana Gigic
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Alexis B. Ulrich
- Pathologisches Institut, University Hospital Heidelberg, 69120 Heidelberg, Germany; (E.H.); (P.S.); (M.K.); (M.v.K.-D.); (J.N.); (H.-U.K.); (B.G.); (A.B.U.)
| | - Adetunji T. Toriola
- Department of Surgery, Washington University St. Louis, St. Louis, MO 63130, USA; (M.M.); (C.B.); (D.C.); (A.T.T.)
| | - Erin M. Siegel
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; (S.F.); (J.S.); (S.D.); (D.C.); (S.L.S.); (E.M.S.)
| | - Christopher I. Li
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
| | - Cornelia M. Ulrich
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Sheetal Hardikar
- Huntsman Cancer Institute, Salt Lake City, UT 84112, USA; (C.H.); (J.O.); (T.L.); (L.C.H.); (A.R.P.); (C.L.S.); (B.P.); (L.L.); (J.N.C.); (M.B.); (E.S.); (J.J.); (C.M.U.)
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT 84112, USA
- Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; (M.S.); (S.A.C.); (U.W.); (W.M.G.); (P.D.L.); (D.R.); (M.K.); (R.M.); (C.I.L.)
- Correspondence: ; Tel.: +1-(801)-213-6238
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Schumacher AJ, Chen Q, Attaluri V, McLemore EC, Chao CR. Metabolic Risk Factors Associated with Early-Onset Colorectal Adenocarcinoma: A Case-Control Study at Kaiser Permanente Southern California. Cancer Epidemiol Biomarkers Prev 2021; 30:1792-1798. [PMID: 34301728 DOI: 10.1158/1055-9965.epi-20-1127] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 02/22/2021] [Accepted: 07/07/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The incidence of early-onset colorectal cancer (eoCRC) diagnosed among individuals under age 50 has been rising. However, risk factors for eoCRC are unclear. We investigated whether metabolic abnormalities are risk factors for eoCRC adenocarcinoma. METHODS Invasive colorectal adenocarcinoma cases diagnosed between ages 15 and 49 from 2008 to 2018 at Kaiser Permanente Southern California (KPSC) were identified. Those with a history of inflammatory bowel disease were excluded. Noncancer controls were selected 5:1 for each case matched by age, sex, and length of membership prior to index date. Data were collected from KSPC's electronic medical records. The exposures of interest included obesity, type II diabetes, hypertension, and dyslipidemia, assessed from ≥1 year prior to eoCRC diagnosis/index date. Conditional logistic regressions were used to evaluate the associations between these metabolic risk factors and risk of eoCRC adenocarcinoma, adjusting for race/ethnicity, smoking, family history, neighborhood socioeconomic status, and health care utilization. RESULTS A total of 1,032 cases and 5,128 controls were included. Risk of colorectal adenocarcinoma was significantly associated with obesity [odds ratio (OR) = 1.41; 95% confidence interval (CI), 1.15-1.74], but not diabetes, hypertension or dyslipidemia. In analysis stratified by tumor location, obesity was significantly associated with risk of colon adenocarcinoma OR = 1.56 (1.17-2.07), but its association with rectal adenocarcinoma was less clear OR = 1.19 (0.85-1.68). No significant interaction was detected between obesity and age (≥40 vs. <40), and obesity and sex. CONCLUSIONS Obesity was associated with risk for eoCRC adenocarcinoma. IMPACT This finding could help inform early-onset colorectal adenocarcinoma screening and prevention recommendations.See related commentary by Hayes, p. xxx.
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Affiliation(s)
- Andrew J Schumacher
- Department of Radiation Oncology, Torrance Memorial Medical Center, Torrance, California
| | - Qiaoling Chen
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Vikram Attaluri
- Department of General Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California
| | - Elisabeth C McLemore
- Department of General Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California
| | - Chun R Chao
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.
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Tang CT, Guo ZX, Wang P, Chen YX, Zeng CY. Higher LNM rate and poorer prognosis of early-onset compared to late-onset T1 stage colorectal cancer: a large-population based study. Am J Cancer Res 2021; 11:3176-3188. [PMID: 34249453 PMCID: PMC8263633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 03/17/2021] [Indexed: 06/13/2023] Open
Abstract
As for T1 stage CRC, there is little knowledge of differences in lymph node metastasis (LNM) and prognosis between early-onset and late-onset CRC. To know that, we included 13,084 patients from the SEER database and 476 patients in T1 stage from our hospital to analyze difference of LNM and prognosis. Univariate and multivariate logistic analyses revealed that early-onset CRC was more likely than late-onset CRC to be positive for LNM. In addition, we found that T1b stage, poor differentiation and lymphatic invasion were risk factors for LNM. Specifically, we found that black race was a risk factor. Before propensity-score matching (PSM), we also found that early-onset CRC patients had better survival, as demonstrated by SEER data. After adjusting for confounding factors by PSM, we found that early onset remained a risk factor for LNM. Moreover, we found that patients diagnosed with early-onset CRC had a poorer prognosis than those diagnosed with late-onset CRC, which was demonstrated by analysis of SEER data and our own data. In conclusion, our study was the first to find that early-onset T1 stage CRC more frequently developed LNM, suggesting that endoscopic submucosal resection should be performed more carefully in these patients. Moreover, early-onset patients in the T1 stage also had poorer survival, suggesting that clinical doctors should pay more attention to early-onset patients.
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Affiliation(s)
- Chao-Tao Tang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Zi-Xiang Guo
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Peng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - You-Xiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
| | - Chun-Yan Zeng
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University Nanchang, China
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Chang VC, Cotterchio M, De P, Tinmouth J. Risk factors for early-onset colorectal cancer: a population-based case-control study in Ontario, Canada. Cancer Causes Control 2021; 32:1063-1083. [PMID: 34120288 PMCID: PMC8416813 DOI: 10.1007/s10552-021-01456-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 05/30/2021] [Indexed: 02/06/2023]
Abstract
Purpose There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged < 50 years, and factors driving this upward trend are unknown. This study investigated associations between various medical, lifestyle, and dietary factors and risk of early-onset CRC (EO-CRC). Methods A population-based case–control study was conducted in Ontario, Canada during 2018–2019. EO-CRC cases aged 20–49 years (n = 175) were identified from the Ontario Cancer Registry; sex- and age group-matched controls (n = 253) were recruited through random digit dialing. Data on potential a priori risk factors were collected using a web-based self-reported questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results Family history of CRC in a first- or second-degree relative (OR 2.37; 95% CI 1.47–3.84), longer sedentary time (≥ 10 vs. < 5 h/day, OR 1.93; 95% CI 1.02–3.65), greater consumption of sugary drinks (≥ 7 vs. < 1 drinks/week, OR 2.99; 95% CI 1.57–5.68), and a more Westernized dietary pattern (quartile 4 vs. 1, OR 1.92; 95% CI 1.01–3.66) were each associated with an increased risk of EO-CRC. Conversely, calcium supplement use (OR 0.53; 95% CI 0.31–0.92), history of allergy or asthma (OR 0.62; 95% CI 0.39–0.98), and greater parity in females (≥ 3 vs. nulliparity, OR 0.29; 95% CI 0.11–0.76) were each associated with a reduced risk. Conclusion Modifiable factors, particularly sedentary behavior and unhealthy diet including sugary drink consumption, may be associated with EO-CRC risk. Our findings, if replicated, may help inform prevention strategies targeted at younger persons. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-021-01456-8.
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Affiliation(s)
- Vicky C Chang
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada.
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
| | - Michelle Cotterchio
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Prithwish De
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
| | - Jill Tinmouth
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, ON, Canada
- Department of Medicine, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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Archambault AN, Lin Y, Jeon J, Harrison TA, Bishop DT, Brenner H, Casey G, Chan AT, Chang-Claude J, Figueiredo JC, Gallinger S, Gruber SB, Gunter MJ, Hoffmeister M, Jenkins MA, Keku TO, Marchand LL, Li L, Moreno V, Newcomb PA, Pai R, Parfrey PS, Rennert G, Sakoda LC, Sandler RS, Slattery ML, Song M, Win AK, Woods MO, Murphy N, Campbell PT, Su YR, Zeleniuch-Jacquotte A, Liang PS, Du M, Hsu L, Peters U, Hayes RB. Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer. JNCI Cancer Spectr 2021; 5:pkab029. [PMID: 34041438 PMCID: PMC8134523 DOI: 10.1093/jncics/pkab029] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/12/2021] [Accepted: 01/27/2021] [Indexed: 12/31/2022] Open
Abstract
Background Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04). Conclusion In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.
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Affiliation(s)
- Alexi N Archambault
- Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA
| | - Yi Lin
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Jihyoun Jeon
- Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
| | - Tabitha A Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - D Timothy Bishop
- Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Graham Casey
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Broad Institute of Harvard and MIT, Cambridge, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany
| | - Jane C Figueiredo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Steven Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Stephen B Gruber
- Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA
| | - Marc J Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Temitope O Keku
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Loïc Le Marchand
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
| | - Li Li
- Department of Family Medicine, University of Virginia, Charlottesville, VA, USA
| | - Victor Moreno
- Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
- ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
| | - Polly A Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- School of Public Health, University of Washington, Seattle, WA, USA
| | - Rish Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | | | - Gad Rennert
- Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel
- Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Clalit National Cancer Control Center, Haifa, Israel
| | - Lori C Sakoda
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Robert S Sandler
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Martha L Slattery
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
| | - Mingyang Song
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Aung Ko Win
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia
| | - Michael O Woods
- Memorial University of Newfoundland, Discipline of Genetics, St John’s, Canada
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Peter T Campbell
- Department of Population Science, American Cancer Society, Atlanta, GA, USA
| | - Yu-Ru Su
- Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Anne Zeleniuch-Jacquotte
- Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA
| | - Peter S Liang
- Department of Medicine, New York University School of Medicine, New York, NY, USA
| | - Mengmeng Du
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Li Hsu
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA
| | - Richard B Hayes
- Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA
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Behavioral Risk Factors and Risk of Early-Onset Colorectal Cancer: Review of the Mechanistic and Observational Evidence. CURRENT COLORECTAL CANCER REPORTS 2021. [DOI: 10.1007/s11888-021-00465-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Fangman BD, Goksu SY, Chowattukunnel N, Beg MS, Sanford NN, Sanjeevaiah A, Cox J, Folkert MR, Aguilera TA, Mathews J, Pogacnik JS, Khatri G, Olson C, Polanco PM, Verma U, Hsiehchen D, Jones A, Kainthla R, Kazmi SM. Disparities in Characteristics, Access to Care, and Oncologic Outcomes in Young-Onset Colorectal Cancer at a Safety-Net Hospital. JCO Oncol Pract 2021; 17:e614-e622. [PMID: 33428470 PMCID: PMC8120665 DOI: 10.1200/op.20.00777] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 10/09/2020] [Accepted: 11/09/2020] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Young-onset colorectal cancer is an emerging cause of significant morbidity and mortality globally. Despite this, limited data exist regarding clinical characteristics and outcomes, particularly in safety-net populations where access to care is limited. We aimed to study disparities in clinical characteristics and outcomes in patients with young-onset colorectal cancer in the safety-net setting. METHODS We performed a retrospective review of patients < 50 years old diagnosed and/or treated for colorectal cancer between 2001 and 2017 at a safety-net hospital. Kaplan-Meier and Cox regression models were constructed to compare overall survival (OS), progression-free survival (PFS), and relapse-free survival (RFS) by race and ethnicity, stratifying for relevant clinical and pathologic factors. RESULTS A total of 395 young-onset patients diagnosed at a safety-net hospital were identified and 270 were included in the analysis (49.6% Hispanic, 25.9% non-Hispanic Black, 20.0% non-Hispanic White, and 4.4% other). Non-Hispanic White race was independently associated with worse OS (hazzard ratio [HR], 0.53; 95% CI, 0.29 to 0.97), as were lack of insurance, higher clinical stage, and mismatch repair proficiency. There was no significant difference seen in PFS or RFS between racial and ethnic groups. CONCLUSION Non-Hispanic White race or ethnicity was found to be independently associated with worse OS in a safety-net population of patients with young-onset colorectal cancer. Other independent predictors of worse OS include higher stage, lack of insurance, and mismatch repair proficiency.
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Affiliation(s)
| | - Suleyman Y. Goksu
- Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | | | - Muhammad S. Beg
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Nina N. Sanford
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Aravind Sanjeevaiah
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - John Cox
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Michael R. Folkert
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Todd A. Aguilera
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Joselin Mathews
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX
| | | | - Gaurav Khatri
- Department of Radiology, UT Southwestern Medical Center, Dallas, TX
| | - Craig Olson
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX
| | | | - Udit Verma
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - David Hsiehchen
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Amy Jones
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Radhika Kainthla
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
| | - Syed M. Kazmi
- Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX
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Menichelli D, Vicario T, Ameri P, Toma M, Violi F, Pignatelli P, Pastori D. Cancer and atrial fibrillation: Epidemiology, mechanisms, and anticoagulation treatment. Prog Cardiovasc Dis 2021; 66:28-36. [PMID: 33915139 DOI: 10.1016/j.pcad.2021.04.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 04/21/2021] [Indexed: 12/14/2022]
Abstract
Cancer patients are at an increased risk of developing atrial fibrillation (AF) and thrombosis. However, the management of anticoagulation in patients with both diseases may be challenging, and data on these patients are lacking. We summarize the current evidence on the incidence and prevalence of cancer in AF and vice versa and provide some practical considerations on the management of oral anticoagulation in specific clinical situations. Low-molecular weight heparins are not approved for thromboprophylaxis in AF, and management of warfarin can be difficult. The use of direct oral anticoagulants may be particularly attractive for their rapid onset/offset action and lower bleeding risk.
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Affiliation(s)
- Danilo Menichelli
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Tommasa Vicario
- Department of General Surgery and Surgical Specialties "Paride Stefanini", Sapienza University of Rome, Rome, Italy; Emergency Department, Policlinico Tor Vergata Hospital, Rome, Italy
| | - Pietro Ameri
- Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine, University of Genova, Genova, Italy
| | - Matteo Toma
- Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine, University of Genova, Genova, Italy
| | - Francesco Violi
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro, Naples, Italy
| | - Pasquale Pignatelli
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy; Mediterranea Cardiocentro, Naples, Italy
| | - Daniele Pastori
- Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
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László L, Kurilla A, Takács T, Kudlik G, Koprivanacz K, Buday L, Vas V. Recent Updates on the Significance of KRAS Mutations in Colorectal Cancer Biology. Cells 2021; 10:667. [PMID: 33802849 PMCID: PMC8002639 DOI: 10.3390/cells10030667] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/03/2021] [Accepted: 03/10/2021] [Indexed: 12/17/2022] Open
Abstract
The most commonly mutated isoform of RAS among all cancer subtypes is KRAS. In this review, we focus on the special role of KRAS mutations in colorectal cancer (CRC), aiming to collect recent data on KRAS-driven enhanced cell signalling, in vitro and in vivo research models, and CRC development-related processes such as metastasis and cancer stem cell formation. We attempt to cover the diverse nature of the effects of KRAS mutations on age-related CRC development. As the incidence of CRC is rising in young adults, we have reviewed the driving forces of ageing-dependent CRC.
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Affiliation(s)
- Loretta László
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
| | - Anita Kurilla
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
| | - Tamás Takács
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
| | - Gyöngyi Kudlik
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
| | - Kitti Koprivanacz
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
| | - László Buday
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
- Department of Medical Chemistry, Semmelweis University Medical School, 1071 Budapest, Hungary
| | - Virag Vas
- Research Centre for Natural Sciences, Institute of Enzymology, 1051 Budapest, Hungary; (L.L.); (A.K.); (T.T.); (G.K.); (K.K.); (L.B.)
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Burnett-Hartman AN, Lee JK, Demb J, Gupta S. An Update on the Epidemiology, Molecular Characterization, Diagnosis, and Screening Strategies for Early-Onset Colorectal Cancer. Gastroenterology 2021; 160:1041-1049. [PMID: 33417940 PMCID: PMC8273929 DOI: 10.1053/j.gastro.2020.12.068] [Citation(s) in RCA: 164] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/22/2020] [Accepted: 12/26/2020] [Indexed: 12/15/2022]
Abstract
Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.
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Affiliation(s)
| | - Jeffrey K Lee
- Division of Research, Kaiser Permanente Northern California; Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California.
| | - Joshua Demb
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla, California
| | - Samir Gupta
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla, California; VA San Diego Healthcare System, San Diego, California
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Demb J, Liu L, Murphy CC, Doubeni CA, Martínez ME, Gupta S. Young-onset colorectal cancer risk among individuals with iron-deficiency anaemia and haematochezia. Gut 2020; 70:gutjnl-2020-321849. [PMID: 33443020 PMCID: PMC8284839 DOI: 10.1136/gutjnl-2020-321849] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Young-onset colorectal cancer (YCRC) incidence is rising. Scant data exist on YCRC risk after presentation with concerning symptoms such as iron-deficiency anaemia (IDA) or haematochezia. We examined the association between IDA and YCRC, and haematochezia and YCRC. DESIGN Cohort study of US Veterans aged 18-49 years receiving Veterans Health Administration (VHA) care 1999-2016. IDA analytic cohort was created matching individuals without incident IDA to those with IDA 4:1 based on sex, birth year and first VHA visit date (n=239 000). We used this approach to also create a distinct haematochezia analytic cohort (n=653 740). Incident YCRC was ascertained via linkage to cancer registry and/or cause-specific mortality data. We computed cumulative incidence, risk difference (RD) and HRs using Cox models in each cohort. RESULTS Five-year YCRC cumulative incidence was 0.45% among individuals with IDA versus 0.05% without IDA (RD: 0.39%, 95% CI: 0.33%-0.46%), corresponding to an HR of 10.81 (95% CI: 8.15-14.33). Comparing IDA versus no IDA, RD was 0.78% for men (95% CI: 0.64%-0.92%) and 0.08% for women (95% CI: 0.03%-0.13%), and RD increased by age from 0.14% for <30 years to 0.53% for 40-49 years. YCRC cumulative incidence was 0.33% among individuals with haematochezia versus 0.03% without haematochezia (RD: 0.30%, 95% CI: 0.26%-0.33%), corresponding to an HR of 10.66 (95% CI: 8.76-12.97). Comparing haematochezia versus no haematochezia, RD increased by age from 0.04% for <30 years to 0.43% for 40-49 years. CONCLUSION Colonoscopy should be strongly considered in adults aged <50 years with IDA or haematochezia without a clinically confirmed alternate source.
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Affiliation(s)
- Joshua Demb
- Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
| | - Lin Liu
- Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA
| | - Caitlin C Murphy
- Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Chyke A Doubeni
- Center for Health Equity and Community Engagement; Family Medicine, Mayo Clinic Cancer Center; Center for Clinical and Translational Science, Mayo Clinic, Rochester, Minnesota, USA
| | - María Elena Martínez
- Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California, USA
| | - Samir Gupta
- Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Section of Gastroenterology, VA San Diego Healthcare System, San Diego, California, USA
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