|
1
|
Masdor NA, Hod R, Syed Soffian SS, Mohammed Nawi A. Qualitative insights into ecobiosocial factors influencing colorectal cancer risk in Malaysia. Health Psychol Behav Med 2025; 13:2493143. [PMID: 40256261 PMCID: PMC12006936 DOI: 10.1080/21642850.2025.2493143] [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: 09/12/2024] [Accepted: 04/05/2025] [Indexed: 04/22/2025] Open
Abstract
Introduction Colorectal cancer (CRC) is a growing public health concern in Malaysia influenced by a complex interplay of ecological, biological, and social (EBS) factors. Despite its increasing incidence, limited research has explored how these factors interact to shape CRC risk in the Malaysian context, especially from the perspectives of affected individuals. This study explores Malaysians' perceptions and experiences regarding CRC risk within the EBS framework. Methods A qualitative case study approach involved in-depth interviews with twelve Malaysians aged 35-75 who had undergone colonoscopy at a university hospital. All interviews were recorded and transcribed. Data were collected until saturation was achieved. The transcripts were coded and analysed using ATLAS.ti software. The data were analysed using thematic analysis. Results Findings revealed key themes related to ecological factors in the physical activity environment, which included the sub-themes of type, facilitators, barriers to physical activity, and food sources. The biological factors theme revealed that a family history of CRC influences experience and perception. The subthemes of social factors were sociocultural customs, misconceptions, food preparation methods, CRC-related foods, and food affordability. Conclusion The findings highlighted the multifactorial nature of CRC risk. Understanding the aspects of EBS supports the development of targeted public health interventions to address modifiable CRC risk factors and promote prevention and early CRC detection in the Malaysian context.
Collapse
Affiliation(s)
- Noor Azreen Masdor
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Rozita Hod
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | | | - Azmawati Mohammed Nawi
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| |
Collapse
|
|
2
|
Ma Y, Ni J, Mei P, Chen Y, Guo X. The burden of colorectal cancer attributable to diet low in whole grains from 1990 to 2021: a global, regional and national analysis. Front Nutr 2025; 12:1527522. [PMID: 40271437 PMCID: PMC12014444 DOI: 10.3389/fnut.2025.1527522] [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: 11/13/2024] [Accepted: 03/25/2025] [Indexed: 04/25/2025] Open
Abstract
Background Colorectal cancer (CRC) is a major global health issue, with rising incidence and mortality rates. Dietary factors, especially whole grains consumption, are critical in determining CRC risk. Understanding CRC deaths and disability-adjusted life years (DALYs) related to low whole grains diets is important for prevention. The purpose of the study is to investigate temporal and geographic trends in CRC deaths and DALYs attributable to diet low in whole grains at the global, regional, and national levels from 1990 to 2021. Methods The data on CRC burden attributable to diet low in whole grains from 1990 to 2021 were extracted from the Global Burden of Diseases (GBD) 2021 database. We described the CRC burden attributable to diet low in whole grains across various years, genders, age groups (5-year age groups from 25 to 94 years and 95+ years), different Socio-demographic Index (SDI) regions and countries. To illustrate the temporal trends in the burden of CRC, we calculated the estimated annual percentage change (EAPC) from 1990 to 2021. Results From 1990 to 2021, the global number of CRC deaths attributable to diet low in whole grains increased from 101,813 (95% UI: 42,588 to 151,170) to 186,257 (95% UI: 76,127 to 284,803), representing a 82.94% growth. Similarly, the number of DALYs increased from 2,540,867 (95% UI: 1,050,794 to 3,754,416) to 4,327,219 (95% UI: 1,754,865 to 6,578,232), representing a 70.30% growth. However, both the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) exhibited a decline, with an EAPC of -0.82 (95% CI: -0.85 to -0.78) and - 0.84 (95% CI: -0.87 to -0.81), respectively. The disease burden is heavier in high SDI and high-middle SDI regions. However, between 1990 and 2021, the only region where both ASMR and ASDR increased was low-middle SDI, while in all other regions, they showed a declining trend. In 2021, East Asia had the highest number of CRC deaths and DALYs attributable to diet low in whole grains at the regional level, followed by Western Europe and High-income North America. Additionally, the burden is greater among males and the elderly. Between 1990 and 2021, the number of CRC deaths attributable to diet low in whole grains rose by 102.13% among males and by 63.20% among females. Generally, both the global age-specific mortality rate and the DALYs rate tend to increase with age. SDI demonstrates a nonlinear "S"-shaped correlation with both ASMR and ASDR of CRC attributable to diet low in whole grains. In 2021, the EAPC in ASMR of CRC attributable to diet low in whole grains was negatively associated with SDI (R = -0.402, p < 0.001), reaching the highest EAPC at approximately SDI of 0.51 and the lowest at 0.85. Similarly, the correlation between EAPC in ASDR and SDI in 2021 exhibited a similar pattern. Conclusion Despite a decline in the ASMR and ASDR of CRC attributable to diet low in whole grains from 1990 to 2021 globally, the absolute number of cases continues to increase, with a particularly notable burden observed in High-middle and High SDI regions, as well as among males and the elderly population. It is imperative to intensify efforts in CRC prevention and health education, specifically targeting these high-risk groups to raise public awareness and consumption of whole grains. Furthermore, screening initiatives should be intensified among these demographics to address the elevated risk of CRC mortality due to insufficient whole grains consumption.
Collapse
Affiliation(s)
- Yuting Ma
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jinghuai Ni
- Department of Bone injury of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Pingping Mei
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Chen
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiutian Guo
- Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| |
Collapse
|
|
3
|
Tembo P, Zhao L, Le Marchand L, Wilkens LR, Park SY, Haiman CA, Wirth MD, Hébert JR. Sleep Duration, Dietary Inflammatory Potential, and Obesity in Relation to Colorectal Cancer Incidence in the Multiethnic Cohort. Nutrients 2025; 17:370. [PMID: 39940229 PMCID: PMC11820058 DOI: 10.3390/nu17030370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 01/15/2025] [Accepted: 01/18/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND/OBJECTIVES Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Sleep duration, diet, and obesity have each been identified as modifiable risk factors linked to CRC. However, their joint effect on CRC incidence is underexplored. This study investigated the association between sleep duration and CRC incidence and explored the joint effects of sleep duration, a pro-inflammatory diet, and obesity on CRC incidence in the Multiethnic Cohort (MEC). METHODS This prospective cohort study analyzed 193,027 participants from Hawaii and California enrolled in the MEC between 1993 and 1996. Sleep duration was self-reported and categorized as short (≤6 h), normal (7-8 h), or long (≥9 h). Diet was self-reported via FFQ and inflammatory potential was assessed using the energy-adjusted Dietary Inflammatory Index (E-DII). CRC cases were identified via cancer registries. Cox proportional hazards models estimated the hazard ratios (HRs) for CRC risk. RESULTS After 23.8 years of follow-up, 5825 CRC cases were identified. A pro-inflammatory diet combined with suboptimal sleep increased CRC risk by 12% (short sleep duration, aHR: 1.12; 95% CI: 1.02-1.24) and 22% (long sleep duration, aHR: 1.22, 95% CI: 1.05-1.43). Furthermore, long sleep duration was associated with a 10% increase in CRC risk (aHR: 1.10; 95% CI: 1.01-1.22) compared with normal sleep, while short sleep showed no significant association overall. Obese individuals with short or long sleep had significantly higher CRC risk (short sleep aHR: 1.35; 95% CI: 1.21-1.51; long sleep aHR: 1.36; 95% CI: 1.14-1.64) compared with non-obese individuals with corresponding sleep durations. CONCLUSIONS Long sleep duration and a combination of suboptimal sleep duration and a pro-inflammatory dietary pattern or obesity amplifies the risk.
Collapse
Affiliation(s)
- Penias Tembo
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208, USA; (P.T.); (M.D.W.)
| | - Longgang Zhao
- School of Nursing, Yale University, Orange, CT 06477, USA;
| | - Loïc Le Marchand
- Population Sciences in the Pacific Program, University of Hawai’i Cancer Center, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (L.L.M.); (L.R.W.); (S.-Y.P.)
| | - Lynne R. Wilkens
- Population Sciences in the Pacific Program, University of Hawai’i Cancer Center, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (L.L.M.); (L.R.W.); (S.-Y.P.)
| | - Song-Yi Park
- Population Sciences in the Pacific Program, University of Hawai’i Cancer Center, University of Hawai’i at Mānoa, Honolulu, HI 96822, USA; (L.L.M.); (L.R.W.); (S.-Y.P.)
| | - Christopher A. Haiman
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90007, USA;
| | - Michael D. Wirth
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208, USA; (P.T.); (M.D.W.)
- College of Nursing, University of South Carolina, Columbia, SC 29208, USA
| | - James R. Hébert
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208, USA; (P.T.); (M.D.W.)
- Department of Nutrition, Connecting Health Innovations, LLC, Columbia, SC 29201, USA
| |
Collapse
|
|
4
|
Zhang Z, Wu Z, Zeng Y, Li Y, Feng Y, Gao Z, Chen Y. Association of Methylenetetrahydrofolate Reductase Gene rs1801133 Polymorphism and Controlling Nutritional Status (CONUT) Score with Colorectal Cancer Susceptibility. Int J Gen Med 2024; 17:6281-6290. [PMID: 39712200 PMCID: PMC11662921 DOI: 10.2147/ijgm.s495139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 12/13/2024] [Indexed: 12/24/2024] Open
Abstract
Background Susceptibility to some cancers is linked to methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the Controlling Nutritional Status (CONUT) score in some populations. However, their relationship with susceptibility to colorectal cancer (CRC) susceptibility in the Hakka Chinese population remains unclear. Methods In total, 620 CRC patients and 734 controls were enrolled. MTHFR rs1801133 was genotyped, medical records (age, sex, smoking history, alcohol consumption, hypertension, diabetes mellitus, and family history of cancer, and blood cell parameters) were collected, and the relationship between this information and CRC susceptibility was analyzed. Results There were significant differences in the distribution of CONUT classification (p=0.002), and proportions of history of smoking (p<0.001), hypertension (p<0.001), diabetes mellitus (p<0.001), and family history of cancer (p=0.002) between patients and controls. There were statistically significant differences in MTHFR rs1801133 genotypes distribution (58.7% C/C, 35.5% C/T, and 5.8% T/T in patients vs 65.5%, 31.2%, and 3.3% in controls, p=0.010) and allele distribution (76.5% C, and 23.5% T allele in patients vs 81.1%, and 18.9% in controls, p=0.003) between patients and controls. Logistic regression analysis indicated that non-normal CONUT range (non-normal vs normal, odds ratio (OR): 1.451, 95% confidence interval (CI): 1.119-1.882, p=0.005), and MTHFR rs1801133 variant (C/T + T/T vs C/C, OR: 1.373, 95% CI: 1.091-1.728, p=0.007), older age (≥65 vs <65 years, OR: 1.298, 95% CI: 1.023-1.646, p=0.032), male sex (OR: 1.354, 95% CI: 1.067-1.718, p=0.013), and history of alcohol drinking (OR: 2.232, 95% CI: 1.164-4.282, p=0.016) were independently associated with CRC risk. Conclusion Individuals carried MTHFR rs1801133 variant and with non-normal CONUT range, advanced age, history of alcohol consumption may be at increased CRC risk in the Hakka population.
Collapse
Affiliation(s)
- Zhuoxin Zhang
- Department of Gastrointestinal Surgery, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Zuguang Wu
- Department of Gastrointestinal Surgery, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Yuwen Zeng
- Department of Gastrointestinal Surgery, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Yunlin Li
- Department of Gastrointestinal Surgery, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Yingchuan Feng
- Department of Gastrointestinal Surgery, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Zhen Gao
- Department of Gastrointestinal Surgery, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Yijin Chen
- Department of Gastroenterology, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| |
Collapse
|
|
5
|
Huang YX, Wu JH, Zhao YQ, Sui WN, Tian T, Han WX, Ni J. An atlas on risk factors for gastrointestinal cancers: A systematic review of Mendelian randomization studies. Prev Med 2024; 189:108147. [PMID: 39368643 DOI: 10.1016/j.ypmed.2024.108147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 09/27/2024] [Accepted: 09/28/2024] [Indexed: 10/07/2024]
Abstract
OBJECTIVE Gastrointestinal cancers are one of the most frequent cancer types and seriously threaten human life and health. Recent studies attribute the occurrence of gastrointestinal cancers to both genetic and environmental factors, yet the intrinsic etiology remains unclear. Mendelian randomization is a powerful well-established statistical method that is based on genome-wide association study (GWAS) to evaluate the causal relationship between exposures and outcomes. In the present study, we aimed to conduct a systematic review of Mendelian randomization studies investigating any causal risk factors for gastrointestinal cancers. METHODS We systematically searched Mendelian randomization studies that addressed the associations of genetically predicted exposures with five main gastrointestinal cancers from September 2014 to March 2024, as well as testing the research quality and validity. RESULTS Our findings suggested robust and consistent causal effects of body mass index (BMI), basal metabolic rate, fatty acids, total cholesterol, total bilirubin, insulin like growth factor-1, eosinophil counts, interleukin 2, alcohol consumption, coffee consumption, apolipoprotein B on colorectal cancer risks, BMI, waist circumference, low-density lipoprotein (LDL), total testosterone, smoking on gastric cancer risks, BMI, fasting insulin, LDL, waist circumference, visceral adipose tissue (VAT), immune cells, type 2 diabetes mellitus (T2DM) on pancreatic cancer risks, waist circumference, smoking, T2DM on esophageal adenocarcinoma risks, and VAT, ferritin, transferrin, alcohol consumption, hepatitis B virus infection, rheumatoid arthritis on liver cancer risks, respectively. CONCLUSION Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.
Collapse
Affiliation(s)
- Yi-Xuan Huang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Jun-Hua Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Yu-Qiang Zhao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Wan-Nian Sui
- Department of Gastrointestinal Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Tian Tian
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China
| | - Wen-Xiu Han
- Department of Gastrointestinal Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
| | - Jing Ni
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
| |
Collapse
|
|
6
|
Li H, Huang HQ, Huang ZG, He RQ, Fang YY, Song R, Luo JY, Zeng DT, Qin K, Wei DM, Chen G. Potential regulatory mechanism and clinical significance of synaptotagmin binding cytoplasmic RNA interacting protein in colorectal cancer. World J Clin Oncol 2024; 15:1412-1427. [PMID: 39582611 PMCID: PMC11514426 DOI: 10.5306/wjco.v15.i11.1412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 08/17/2024] [Accepted: 09/09/2024] [Indexed: 10/14/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) causes many deaths worldwide. Synaptotagmin binding cytoplasmic RNA interacting protein (SYNCRIP) is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes. Our study will examine the expression, potential effect, biological function and clinical value of SYNCRIP in CRC. AIM To examine the expression, potential effect, biological function and clinical value of SYNCRIP in CRC. METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data. The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology. The target genes of SYNCRIP were calculated using various algorithms, and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis. The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods. RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples. Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene. SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment. In addition, CRC patients with high SYNCRIP expression are more sensitive to radiotherapy. CONCLUSION SYNCRIP is upregulated in CRC, and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects. In addition, SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy.
Collapse
Affiliation(s)
- Hui Li
- Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - He-Qing Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Guang Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Rong-Quan He
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ye-Ying Fang
- Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Rui Song
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jia-Yuan Luo
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Da-Tong Zeng
- Department of Pathology, Redcross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
| | - Kai Qin
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Dan-Ming Wei
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
|
7
|
Liang L, Guo X, Ye W, Liu Y. KRAS Gene Mutation Associated with Grade of Tumor Budding and Peripheral Immunoinflammatory Indices in Patients with Colorectal Cancer. Int J Gen Med 2024; 17:4769-4780. [PMID: 39440104 PMCID: PMC11495189 DOI: 10.2147/ijgm.s487525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024] Open
Abstract
Background The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC. Methods Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed. Results 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287-3.016, p=0.002), and high SII level (≥807.81 vs <807.81, OR: 1.915, 95% CI: 1.120-3.272, p=0.018) were independently associated with KRAS mutation. Conclusion Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.
Collapse
Affiliation(s)
- Liu Liang
- Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Xuemin Guo
- Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Wei Ye
- Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| | - Yuxiang Liu
- Department of Medical Oncology, Meizhou People’s Hospital, Meizhou, People’s Republic of China
| |
Collapse
|
|
8
|
Shanmugam R, Majee P, Shi W, Ozturk MB, Vaiyapuri TS, Idzham K, Raju A, Shin SH, Fidan K, Low JL, Chua JY, Kong YC, Qi OY, Tan E, Chok AY, Seow-En I, Wee I, Macalinao DC, Chong DQ, Chang HY, Lee F, Leow WQ, Murata-Hori M, Xiaoqian Z, Shumei C, Tan CS, Dasgupta R, Tan IB, Tergaonkar V. Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers. Cancer Discov 2024; 14:1940-1963. [PMID: 38885349 PMCID: PMC11450372 DOI: 10.1158/2159-8290.cd-23-1379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 04/15/2024] [Accepted: 06/12/2024] [Indexed: 06/20/2024]
Abstract
Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with an increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by reactivating the dormant human telomerase reverse transcriptase (hTERT) subunit of the telomerase holoenzyme in an iron-(Fe3+)-dependent manner and thereby drives colorectal cancers. Chemical genetic screens combined with isothermal dose-response fingerprinting and mass spectrometry identified a small molecule SP2509 that specifically inhibits Pirin-mediated hTERT reactivation in colorectal cancers by competing with iron-(Fe3+) binding. Our findings, first to document how metal ions reactivate telomerase, provide a molecular mechanism for the well-known association between red meat and increased incidence of colorectal cancers. Small molecules like SP2509 represent a novel modality to target telomerase that acts as a driver of 90% of human cancers and is yet to be targeted in clinic. Significance: We show how iron-(Fe3+) in collusion with genetic factors reactivates telomerase, providing a molecular mechanism for the association between iron overload and increased incidence of colorectal cancers. Although no enzymatic inhibitors of telomerase have entered the clinic, we identify SP2509, a small molecule that targets telomerase reactivation and function in colorectal cancers.
Collapse
Affiliation(s)
- Raghuvaran Shanmugam
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Prativa Majee
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Wei Shi
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Mert B. Ozturk
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Thamil S. Vaiyapuri
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Khaireen Idzham
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Anandhkumar Raju
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Seung H. Shin
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Kerem Fidan
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Joo-Leng Low
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Joelle Y.H. Chua
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Yap C. Kong
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Ong Y. Qi
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
| | - Emile Tan
- Department of Colorectal Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
| | - Aik Y. Chok
- Department of Colorectal Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
| | - Isaac Seow-En
- Department of Colorectal Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
| | - Ian Wee
- Department of Colorectal Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
| | - Dominique C. Macalinao
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
| | - Dawn Q. Chong
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
| | - Hong Y. Chang
- Experimental Drug Development Center, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Fiona Lee
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Wei Q. Leow
- Department of Colorectal Surgery, Singapore General Hospital, Singapore, Republic of Singapore.
| | - Maki Murata-Hori
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Zhang Xiaoqian
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Chia Shumei
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Chris S.H. Tan
- Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, China.
| | - Ramanuj Dasgupta
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
| | - Iain B. Tan
- Genome Institute of Singapore, Agency for Science, Technology, and Research (A*STAR), Singapore, Republic of Singapore.
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Republic of Singapore.
- Cancer and Stem Cell Biology, Duke-National University of Singapore, Singapore, Republic of Singapore.
| | - Vinay Tergaonkar
- Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Republic of Singapore.
| |
Collapse
|
|
9
|
Bricca L, Porcari S, Savarino E, Rugge M. Microbiota in gastrointestinal malignancies. Best Pract Res Clin Gastroenterol 2024; 72:101953. [PMID: 39645287 DOI: 10.1016/j.bpg.2024.101953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 10/05/2024] [Accepted: 10/09/2024] [Indexed: 12/09/2024]
Abstract
This manuscript provides an overview of the microbiota profile associated with precancerous lesions in the esophagus, stomach, and large bowel. The critical review of the available data reveals significant variability in the methods used for microbiota profiling. This variability may affect the reliable identification of specific biological links between histologically profiled neoplastic diseases and the microbiota population. Overall, this critical review reveals significant links between microbiota communities and the different lesions within the spectrum of the oncogenetic cascade in various epidemiological contexts and anatomical districts.
Collapse
Affiliation(s)
- Ludovica Bricca
- Department of Surgical Oncological and Gastroenterological Science (DiSCOG), Gastroenterology Unit, University of Padova, Padova, Italy
| | - Serena Porcari
- Department of Medical and Surgical Sciences, University Cattolica del Sacro Cuore - IRCCS Policlinico A. Gemelli, Roma, Italy
| | - Edoardo Savarino
- Department of Surgical Oncological and Gastroenterological Science (DiSCOG), Gastroenterology Unit, University of Padova, Padova, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy.
| |
Collapse
|
|
10
|
An S, Gunathilake M, Lee J, Kim M, Oh JH, Chang HJ, Sohn DK, Shin A, Kim J. Relationship Between Aspirin Use and Site-Specific Colorectal Cancer Risk Among Individuals With Metabolic Comorbidity. J Korean Med Sci 2024; 39:e199. [PMID: 38978486 PMCID: PMC11231443 DOI: 10.3346/jkms.2024.39.e199] [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: 12/15/2023] [Accepted: 05/22/2024] [Indexed: 07/10/2024] Open
Abstract
BACKGROUND The relationship between aspirin usage and the risk of colorectal cancer (CRC) among individuals with both hypertension (HTN) and diabetes mellitus (DM) remains unclear. This study aims to explore the impact of aspirin use on the site-specific CRC risk in patients with metabolic comorbidity. METHODS A case-control study was conducted among 1,331 CRC patients and 2,771 controls recruited from the Nation Cancer Center in Korea. Multinomial logistic regression analyses were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between aspirin use, metabolic disease status, and site-specific CRC risk. RESULTS Among the 4,102 participants, 1,191 individuals had neither HTN nor DM, 2,044 were diagnosed with HTN, 203 with DM, and 664 presented with HTN and DM comorbidity. An increasing number of HTN and DM was associated with an increased risk of overall CRC (HTN or DM: OR, 1.70; 95% CI, 1.39-2.07; HTN and DM: OR, 8.43; 95% CI, 6.37-11.16), while aspirin use was associated with a decreased risk of overall CRC (OR, 0.31; 95% CI, 0.21-0.46). These results remained consistent across anatomical sites. Among individuals with HTN and DM comorbidity, aspirin use notably associated with lower risk of overall CRC (OR, 0.39; 95% CI, 0.21-0.72), proximal colon (OR, 0.32; 95% CI, 0.13-0.71) and rectal cancer (OR, 0.27; 95% CI, 0.08-0.97), but not distal colon cancer (OR, 0.58; 95% CI, 0.27-1.24). CONCLUSION This study showed that aspirin use is negatively associated with overall and site-specific CRC, even among individuals with HTN and DM comorbidity.
Collapse
Affiliation(s)
- Seokyung An
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Madhawa Gunathilake
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Minji Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Hee Jin Chang
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Dae Kyung Sohn
- Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
| |
Collapse
|
|
11
|
Lei J, Fu J, Wang T, Guo Y, Gong M, Xia T, Shang S, Xu Y, Cheng L, Lin B. Molecular subtype identification and prognosis stratification by a immunogenic cell death-related gene expression signature in colorectal cancer. Expert Rev Anticancer Ther 2024; 24:635-647. [PMID: 38407877 DOI: 10.1080/14737140.2024.2320187] [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: 08/31/2023] [Accepted: 12/28/2023] [Indexed: 02/27/2024]
Abstract
OBJECTIVES This study intended to develop a new immunogenic cell death (ICD)-related prognostic signature for colorectal cancer (CRC) patients. RESEARCH DESIGN AND METHODS The Non-Negative Matrix Factorization (NMF) algorithm was adopted to cluster tumor samples based on ICD gene expression to obtain ICD-related subtypes. Survival analysis and immune microenvironment analysis were conducted among different subtypes. Regression analysis was used to construct the model. Based on riskscore median, cancer patients were classified into high and low risk groups, and independent prognostic ability of the model was analyzed. The CIBERSORT algorithm was adopted to determine the immune infiltration level of both groups. RESULTS We analyzed the differential genes between cluster 4 and cluster 1-3 and obtained 12 genes with the best prognostic features finally (NLGN1, SLC30A3, C3orf20, ADAD2, ATOH1, ATP6V1B1, KCNQ2, MUCL3, RGCC, CLEC17A, COL6A5, and INSL4). In addition, patients with lower risk had higher levels of infiltration of most immune cells, lower Tumor Immune Dysfunction and Exclusion (TIDE) level and higher immunophenscore (IPS) level than those with higher risk. CONCLUSIONS This study constructed and validated the ICD feature signature predicting CRC prognosis and provide a reference criteria for guiding the prognosis and immunotherapy of CRC cancer patients.
Collapse
Affiliation(s)
- Junping Lei
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Jia Fu
- Department of Pulmonary and Critical Care Medicine, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Tianyang Wang
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Yu Guo
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Mingmin Gong
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Tian Xia
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Song Shang
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Yan Xu
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| | - Ling Cheng
- Zhejiang Luoxi Medical Technology Co. Ltd, Hangzhou, P.R, China
| | - Binghu Lin
- Department of Colorectal and Anal Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, P.R, China
| |
Collapse
|
|
12
|
Tian Y, Lin Y, Qu C, Arndt V, Baurley JW, Berndt SI, Bien SA, Bishop DT, Brenner H, Buchanan DD, Budiarto A, Campbell PT, Carreras-Torres R, Casey G, Chan AT, Chen R, Chen X, Conti DV, Díez-Obrero V, Dimou N, Drew DA, Figueiredo JC, Gallinger S, Giles GG, Gruber SB, Gunter MJ, Harlid S, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Jenkins MA, Jordahl KM, Joshi AD, Keku TO, Kawaguchi E, Kim AE, Kundaje A, Larsson SC, Marchand LL, Lewinger JP, Li L, Moreno V, Morrison J, Murphy N, Nan H, Nassir R, Newcomb PA, Obón-Santacana M, Ogino S, Ose J, Pardamean B, Pellatt AJ, Peoples AR, Platz EA, Potter JD, Prentice RL, Rennert G, Ruiz-Narvaez EA, Sakoda LC, Schoen RE, Shcherbina A, Stern MC, Su YR, Thibodeau SN, Thomas DC, Tsilidis KK, van Duijnhoven FJB, Van Guelpen B, Visvanathan K, White E, Wolk A, Woods MO, Wu AH, Peters U, Gauderman WJ, Hsu L, Chang-Claude J. Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk. Br J Cancer 2024; 130:1687-1696. [PMID: 38561434 PMCID: PMC11091089 DOI: 10.1038/s41416-024-02638-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
Collapse
Affiliation(s)
- Yu Tian
- School of Public Health, Capital Medical University, Beijing, China
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Yi Lin
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Conghui Qu
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Volker Arndt
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - James W Baurley
- Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia
- BioRealm LLC, Walnut, CA, USA
| | - Sonja I Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Stephanie A Bien
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - D Timothy Bishop
- Leeds Institute of Cancer and Pathology, 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
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia
- University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3010, Australia
- Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Arif Budiarto
- Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Robert Carreras-Torres
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute Dr Josep Trueta (IDIBGI), Salt, 17190, Girona, Spain
| | - Graham Casey
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- 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
- 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
| | - Rui Chen
- School of Public Health, Capital Medical University, Beijing, China
| | - Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - David V Conti
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Virginia Díez-Obrero
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Niki Dimou
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - David A Drew
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Jane C Figueiredo
- Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Population and Public Health Sciences, 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, ON, Canada
| | - Graham G Giles
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
| | - Stephen B Gruber
- Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA
| | - Marc J Gunter
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Sophia Harlid
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
| | - Tabitha A Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Akihisa Hidaka
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jeroen R Huyghe
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Kristina M Jordahl
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Amit D Joshi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - Temitope O Keku
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA
| | - Eric Kawaguchi
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Andre E Kim
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Anshul Kundaje
- Department of Genetics, Stanford University, Stanford, CA, USA
- Department of Computer Science, Stanford University, Stanford, CA, USA
| | - Susanna C Larsson
- Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | | | - Juan Pablo Lewinger
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Li Li
- Department of Family Medicine, University of Virginia, Charlottesville, VA, USA
| | - Victor Moreno
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Department of Clinical Sciences, Faculty of Medicine and health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain
| | - John Morrison
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Neil Murphy
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
| | - Hongmei Nan
- Department of Global Health, Richard M. Fairbanks School of Public Health, Indianapolis, IN, USA
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indianapolis, Indianapolis, IN, USA
| | - Rami Nassir
- Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia
| | - Polly A Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Mireia Obón-Santacana
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Shuji Ogino
- 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
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan
| | - Jennifer Ose
- Huntsman Cancer Institute, Salt Lake City, UT, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
- Hochschule Hannover, University of Applied Sciences and Arts, Department III: Media, Information and Design, Hannover, Germany
| | - Bens Pardamean
- Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia
| | - Andrew J Pellatt
- Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Anita R Peoples
- Huntsman Cancer Institute, Salt Lake City, UT, USA
- Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA
| | - Elizabeth A Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - John D Potter
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
- Research Centre for Hauora and Health, Massey University, Wellington, New Zealand
| | - Ross L Prentice
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Biostatistics, University of Washington, Seattle, WA, 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
| | - Edward A Ruiz-Narvaez
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - 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 E Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Anna Shcherbina
- Biomedical Informatics Program, Department of Biomedical Data Sciences, Stanford University, Stanford, CA, USA
| | - Mariana C Stern
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Yu-Ru Su
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
| | - Stephen N Thibodeau
- Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Duncan C Thomas
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Konstantinos K Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | | | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Kala Visvanathan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Emily White
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Alicja Wolk
- Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | - Michael O Woods
- Memorial University of Newfoundland, Discipline of Genetics, St. John's, NL, Canada
| | - Anna H Wu
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - W James Gauderman
- Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Li Hsu
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
- Department of Biostatistics, University of Washington, Seattle, WA, USA.
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- University Cancer Centre Hamburg (UCCH), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
| |
Collapse
|
|
13
|
Li F, Wan X, Li Z, Zhou L. High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K/AKT/mTOR pathway. Cancer Med 2024; 13:e7382. [PMID: 38872380 PMCID: PMC11176572 DOI: 10.1002/cam4.7382] [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: 02/25/2024] [Revised: 05/16/2024] [Accepted: 05/28/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) ranks among the most prevalent malignancies worldwide, characterized by its complex etiology and slow research progress. Diabetes, as an independent risk factor for CRC, has been widely certified. Consequently, this study centers on elucidating the intricacies of CRC cells initiation and progression within a high-glucose environment. METHODS A battery of assays was employed to assess the proliferation and metastasis of CRC cells cultured under varying glucose concentrations. Optimal glucose levels conducive to cells' proliferation and migration were identified. Western blot analyses were conducted to evaluate alterations in apoptosis, autophagy, and EMT-related proteins in CRC cells under high-glucose conditions. The expression of PI3K/AKT/mTOR pathway-associated proteins was assessed using western blot. The effect of high glucose on xenograft growth was investigated in vivo by MC38 cells, and changes in inflammatory factors (IL-4, IL-13, TNF-α, IL-5, and IL-12) were measured via serum ELISA. RESULTS Our experiments demonstrated that elevated glucose concentrations promoted both the proliferation and migration of CRC cells; the most favorable glucose dose is 20 mM. Western blot analyses revealed a decrease in apoptotic proteins, such as Bim, Bax, and caspase-3 with increasing glucose levels. Concurrently, the expression of EMT-related proteins, including N-cadherin, vimentin, ZEB1, and MMP9, increased. High-glucose cultured cells exhibited elevated levels of PI3K/AKT/mTOR pathway proteins. In the xenograft model, tumor cells stimulated by high glucose exhibited accelerated growth, larger tumor volumes, and heightened KI67 expression of immunohistochemistry. ELISA experiments revealed higher expression of IL-4 and IL-13 and lower expression of TNF-α and IL-5 in the serum of high-glucose-stimulated mice. CONCLUSION The most favorable dose and time for tumor cells proliferation and migration is 20 mM, 48 h. High glucose fosters CRC cell proliferation and migration while suppressing autophagy through the activation of the PI3K/AKT/mTOR pathway.
Collapse
Affiliation(s)
- Feng Li
- Department of Pharmacology, West China School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, China
| | - Xing Wan
- Department of Pharmacology, West China School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, China
| | - Zhigui Li
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Liming Zhou
- Department of Pharmacology, West China School of Basic Science and Forensic Medicine, Sichuan University, Chengdu, China
| |
Collapse
|
|
14
|
Moghimipour E, Handali S. Functionalized liposomes as a potential drug delivery systems for colon cancer treatment: A systematic review. Int J Biol Macromol 2024; 269:132023. [PMID: 38697444 DOI: 10.1016/j.ijbiomac.2024.132023] [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: 07/14/2023] [Revised: 04/27/2024] [Accepted: 04/29/2024] [Indexed: 05/05/2024]
Abstract
Colon cancer is one of the lethal diseases in the world with approximately 700,000 fatalities annually. Nowadays, due to the side effects of existing methods in the treatment of colon cancer such as radiotherapy and chemotherapy, the use of targeted nanocarriers in cancer treatment has received wide attention, and among them, especially liposomes have been studied a lot. Based on this, anti-tumor drugs hidden in targeted active liposomes can selectively act on cancer cells. In this systematic review, the use of various ligands such as folic acid, transferrin, aptamer, hyaluronic acid and cRGD for active targeting of liposomes to achieve improved drug delivery to colon cancer cells has been reviewed. The original articles published in English in the databases of Science Direct, PubMed and Google scholar from 2012 to 2022 were reviewed. From the total of 26,256 published articles, 19 studies met the inclusion criteria. The results of in vitro and in vivo studies have revealed that targeted liposomes lead to increasing the efficacy of anti-cancer agents on colon cancer cells with reducing side effects compared to free drugs and non-targeted liposomes. To the best of our knowledge, this is the first systematic review showing promising results for improvement treatment of colon cancer using targeted liposomes.
Collapse
Affiliation(s)
- Eskandar Moghimipour
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Somayeh Handali
- Medical Biomaterials Research Center (MBRC), Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
15
|
Wang X, Guan X, Tong Y, Liang Y, Huang Z, Wen M, Luo J, Chen H, Yang S, She Z, Wei Z, Zhou Y, Qi Y, Zhu P, Nong Y, Zhang Q. UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer. BMC Cancer 2024; 24:644. [PMID: 38802800 PMCID: PMC11129395 DOI: 10.1186/s12885-024-12321-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 04/30/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. METHODS Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. RESULTS Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). CONCLUSIONS To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.
Collapse
Affiliation(s)
- Xuancheng Wang
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Xuan Guan
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Ying Tong
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Yunxiao Liang
- Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, PR China
| | - Zongsheng Huang
- Department of Gastroenterology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, PR China
| | - Mingsen Wen
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Jichu Luo
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Hongwei Chen
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Shanyi Yang
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Zhiyong She
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Zhijuan Wei
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Yun Zhou
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Yali Qi
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Pingchuan Zhu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning, Guangxi, 530004, PR China
| | - Yanying Nong
- Department of Academic Affairs, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, PR China.
| | - Qisong Zhang
- Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, Guangxi, 530004, PR China.
- Center for Instrumental Analysis, Guangxi University, Nanning, Guangxi, 530004, PR China.
| |
Collapse
|
|
16
|
Zou Y, Zhu J, Song C, Li T, Wang K, Shi J, Ye H, Wang P. A polygenetic risk score combined with environmental factors better predict susceptibility to hepatocellular carcinoma in Chinese population. Cancer Med 2024; 13:e7230. [PMID: 38698686 PMCID: PMC11066500 DOI: 10.1002/cam4.7230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/11/2024] [Accepted: 04/18/2024] [Indexed: 05/05/2024] Open
Abstract
AIMS This study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS). METHODS A case-control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta-analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models. RESULTS A total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84-0.89; AUC: 0.85, 95% CI: 0.81-0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60-0.67; AUC: 0.65, 95% CI: 0.60-0.71). CONCLUSIONS A novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at-risk individuals for precise prevention.
Collapse
Affiliation(s)
- Yuanlin Zou
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Jicun Zhu
- Department of PharmacyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Caijuan Song
- The Institution for Chronic and Noncommunicable Disease Control and PreventionZhengzhou Center for Disease Control and PreventionZhengzhouHenan ProvinceChina
| | - Tiandong Li
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Keyan Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Institute of Medical and Pharmaceutical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Jianxiang Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Institute of Medical and Pharmaceutical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Hua Ye
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| | - Peng Wang
- Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouHenan ProvinceChina
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & TreatmentZhengzhou UniversityZhengzhouHenan ProvinceChina
| |
Collapse
|
|
17
|
Novikov DV, Perenkov AD, Shumilova SV, Kubysheva NI, Novikov VV. CD38 gene polymorphism rs1130169 contribution to the increased gene expression and risk of colorectal cancer (pilot study). Mol Biol Rep 2024; 51:63. [PMID: 38170288 DOI: 10.1007/s11033-023-09034-8] [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: 09/27/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Genetic variations in immune signaling genes may have regulatory effect on phenotypic heterogeneity of immune cells and immune functions, hence promoting tumor growth. PURPOSE We compared the frequencies of potentially functional CD38 gene single nucleotide polymorphisms rs1130169 (T > C) in 86 healthy controls and 90 colorectal cancer (CRC) cases to assess their association with cancer risk and CD38 gene expression. RESULTS The association between allele C rs1130169 and CRC risk was observed. Allele C was also significantly correlated with an increased CD38 mRNA level and CD38 positive cell percentages in peripheral blood of healthy controls that could be a possible explanation for CRC risk in C allele carriers. In peripheral blood of CRC patients CD38 mRNA and serum soluble CD38 protein levels significantly differed from those in healthy controls. Calculation of the CD38 full-length and with the third exon deletion mRNA ratio in corresponding samples showed that the mRNA isoform ratio was significantly higher in CRC cases than in controls. It suggests that alternative splicing regulates elevation of CD38 full-length mRNA level in peripheral blood of CRC patients. We also have observed higher expression levels of CD38 full-length mRNA in peripheral blood of CRC patients with lymph node metastases compared to patients without metastases. CONCLUSION This study indicated biological significance of rs1130169 variations that can alter differences in CRC risk by regulating CD38 gene expression.
Collapse
Affiliation(s)
- Dmitry V Novikov
- I.N. Blokhina Research Institute of Epidemiology and Microbiology, Malaya Yamskaya Str. 71, Nizhny Novgorod, Russia, 603950
- Lobachevsky State University of Nizhny Novgorod, Gagarin Str. 23, Nizhny Novgorod, Russia, 603950
| | - Alexei D Perenkov
- Lobachevsky State University of Nizhny Novgorod, Gagarin Str. 23, Nizhny Novgorod, Russia, 603950
| | - Svetlana V Shumilova
- Lobachevsky State University of Nizhny Novgorod, Gagarin Str. 23, Nizhny Novgorod, Russia, 603950
| | | | - Viktor V Novikov
- I.N. Blokhina Research Institute of Epidemiology and Microbiology, Malaya Yamskaya Str. 71, Nizhny Novgorod, Russia, 603950
- Lobachevsky State University of Nizhny Novgorod, Gagarin Str. 23, Nizhny Novgorod, Russia, 603950
| |
Collapse
|
|
18
|
Yu Q, Zhang Y, Tian Y, Peng A, Cui X, Ding B, Yang L, Liu Y, Ju Y, Gao C. Exosomal Circ_FMN2 Derived from the Serum of Colorectal Cancer Patients Promotes Cancer Progression by miR-338-3p/MSI1 Axis. Appl Biochem Biotechnol 2023; 195:7322-7337. [PMID: 36995659 DOI: 10.1007/s12010-023-04456-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2023] [Indexed: 03/31/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract with high incidence and mortality. Exosomal circular RNA (circRNA) has been shown to be associated with the malignant progression of cancers, including CRC. Circ_0005100 (named as circ_FMN2) has been shown to promote CRC cell proliferation and migration. However, whether exosomal circ_FMN2 participated in CRC progression remains unclear. METHODS Exosomes were isolated from the serum of CRC patients and then identified using transmission electron microscope. Western blot assay was used to test the protein levels of exosome markers, proliferation-related marker, metastasis-related markers and musashi-1 (MSI1). The expression levels of circ_FMN2, microRNA (miR)-338-3p and MSI1 were detected by qPCR. Flow cytometry, colony formation assay, MTT assay, and transwell assay were employed to measure cell cycle, apoptosis, colony formation ability, viability, migration and invasion. Dual-luciferase reporter assay was performed to assess the interaction between miR-338-3p and circ_FMN2 or MSI1. BALB/c nude mice was used to conduct animal experiments. RESULTS Circ_FMN2 was overexpressed in the exosomes of CRC patient's serums and CRC cells. Overexpressed exosomal circ_FMN2 could promote CRC cell proliferation, metastasis, and suppress apoptosis. Circ_FMN2 acted as miR-338-3p sponge. MiR-338-3p overexpression reversed the promotion effect of circ_FMN2 on CRC progression. MSI1 was found to be a target of miR-338-3p, and its overexpression revoked the inhibitory effect of miR-338-3p on CRC progression. Furthermore, exosomal circ_FMN2 overexpression also could facilitate CRC tumor growth in vivo. CONCLUSION Exosomal circ_FMN2 accelerated CRC progression through miR-338-3p/MSI1 axis, revealing that exosomal circ_FMN2 might be a target for CRC treatment.
Collapse
Affiliation(s)
- Qiyao Yu
- Department of Research, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yi Zhang
- Department of Physiology, Hebei Medical University, Shijiazhuang, 050011, Hebei Province, China
| | - Yanming Tian
- Department of Physiology, Hebei Medical University, Shijiazhuang, 050011, Hebei Province, China
| | - Ale Peng
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No. 12, Jian Kang Road, Shijiazhuang, 050011, Hebei Province, China
| | - Xiujing Cui
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No. 12, Jian Kang Road, Shijiazhuang, 050011, Hebei Province, China
| | - Boyue Ding
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No. 12, Jian Kang Road, Shijiazhuang, 050011, Hebei Province, China
| | - Lei Yang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No. 12, Jian Kang Road, Shijiazhuang, 050011, Hebei Province, China
| | - Yabin Liu
- Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yingchao Ju
- Department of experimental animal center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Chao Gao
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, No. 12, Jian Kang Road, Shijiazhuang, 050011, Hebei Province, China.
| |
Collapse
|
|
19
|
Ionescu VA, Gheorghe G, Bacalbasa N, Chiotoroiu AL, Diaconu C. Colorectal Cancer: From Risk Factors to Oncogenesis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1646. [PMID: 37763765 PMCID: PMC10537191 DOI: 10.3390/medicina59091646] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/05/2023] [Accepted: 09/09/2023] [Indexed: 09/29/2023]
Abstract
Colorectal cancer is the second leading cause of cancer-related mortality worldwide. Numerous pathophysiological mechanisms, such as abnormal cell proliferation, cell differentiation, resistance to apoptosis, invasion of structures adjacent to colorectal tumor cells, and distant metastasis, are involved in colorectal carcinogenesis. These processes are initiated by the complex interaction of a number of genetic and environmental factors, including sedentary lifestyle, obesity, alcohol consumption, smoking, or gut microbiota. Despite the significant progress achieved in the diagnostic and therapeutic management of patients with colorectal cancer, there has been recently a noteworthy increase in the incidence of colorectal cancer in individuals below the age of 50 years. Early-onset colorectal cancer has a different frequency of oncogenic mutations, a higher prevalence of mucinous histology, a distinct deoxyribonucleic acid (DNA) methylation profile, a more distal location, and lower survival rates. A significant improvement in the prognosis of these patients can be achieved through the detection and removal of modifiable risk factors, along with the implementation of personalized screening strategies for individuals at high risk for this malignancy. Furthermore, gaining comprehension of the pathophysiological mechanisms by which these risk factors contribute to the process of oncogenesis may facilitate the discovery of novel therapeutic targets.
Collapse
Affiliation(s)
- Vlad Alexandru Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (N.B.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department of Cellular and Mollecular Pathology, Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
| | - Gina Gheorghe
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (N.B.)
- Department of Cellular and Mollecular Pathology, Stefan S. Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania
- Gastroenterology Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Nicolae Bacalbasa
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (N.B.)
- Department of Visceral Surgery, Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | | | - Camelia Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (V.A.I.); (N.B.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Academy of Romanian Scientists, 050085 Bucharest, Romania
| |
Collapse
|
|
20
|
Słoka J, Madej M, Strzalka-Mrozik B. Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer. Molecules 2023; 28:5081. [PMID: 37446747 DOI: 10.3390/molecules28135081] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Chemoprevention is one of the ways to fight colorectal cancer, which is a huge challenge in oncology. Numerous pieces of evidence indicate that chronic inflammation in the course of Crohn's disease or ulcerative colitis (UC) is a significant cancer risk factor. Epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), including mesalazine, has beneficial effects on colitis-associated colorectal cancer. Mesalazine is a first-line therapy for UC and is also widely used for maintaining remission in UC. Data showed that mesalazine has antiproliferative properties associated with cyclooxygenase (COX) inhibition but can also act through COX-independent pathways. This review summarizes knowledge about mesalazine's molecular mechanisms of action and chemopreventive effect by which it could interfere with colorectal cancer cell proliferation and survival.
Collapse
Affiliation(s)
- Joanna Słoka
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland
| | - Marcel Madej
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland
| | - Barbara Strzalka-Mrozik
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland
| |
Collapse
|
|
21
|
Dong Z, Shi R, Li P, Song X, Dong F, Zhu J, Wu R, Liang Z, Du M, Wang J, Yang Z. Does postcholecystectomy increase the risk of colorectal cancer? Front Microbiol 2023; 14:1194419. [PMID: 37426004 PMCID: PMC10324655 DOI: 10.3389/fmicb.2023.1194419] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/31/2023] [Indexed: 07/11/2023] Open
Abstract
With the increasing number of cholecystectomy and the high proportion of colorectal cancer in malignant tumors, the question of whether cholecystectomy is a risk factor for colorectal disease has been widely concerned. After reviewing the literature at home and abroad, the authors will summarize the research progress of the correlation between the occurrence of colorectal tumors after cholecystectomy, in order to provide help for the prevention and treatment of colorectal tumors.
Collapse
Affiliation(s)
- Zhenyu Dong
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Ruixian Shi
- Department of Neurology, Baotou Central Hospital, Baotou, Inner Mongolia, China
- Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Pengda Li
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Xiaobiao Song
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Fan Dong
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Jianmin Zhu
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Riga Wu
- Department of General Surgery, The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China
| | - Zhi Liang
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Mingyue Du
- Baotou Medical College, Baotou, Inner Mongolia, China
| | - Jijun Wang
- Department of General Surgery, Baotou Central Hospital, Baotou, Inner Mongolia, China
| | - Zhigang Yang
- Department of Urology, Baotou Central Hospital, Baotou, Inner Mongolia, China
| |
Collapse
|
|
22
|
Rasouli M, Khakshournia S, Vakili O, Dastghaib S, Seghatoleslam A, Shafiee SM. The crosstalk between ubiquitin-conjugating enzyme E2Q1 and p53 in colorectal cancer: An in vitro analysis. Med Oncol 2023; 40:199. [PMID: 37294480 DOI: 10.1007/s12032-023-02039-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/25/2023] [Indexed: 06/10/2023]
Abstract
Colorectal cancer (CRC) is a prevalent gastrointestinal neoplasm that ranks fourth in terms of cancer-related deaths worldwide. In the process of CRC progression, multiple ubiquitin-conjugating enzymes (E2s) are involved; UBE2Q1 is one of those newly identified E2s that is markedly expressed in human colorectal tumors. Since p53 is a well-known tumor suppressor and defined as a key factor to be targeted by the ubiquitin-proteasome system, we hypothesized that UBE2Q1 might contribute to CRC progression through the modulation of p53. Using the lipofection method, the cultured SW480 and LS180 cells were transfected with the UBE2Q1 ORF-containing pCMV6-AN-GFP vector. Then, quantitative RT-PCR was used to assay the mRNA expression levels of p53's target genes, i.e., Mdm2, Bcl2, and Cyclin E. Moreover, Western blot analysis was performed to confirm the cellular overexpression of UBE2Q1 and assess the protein levels of p53, pre- and post-transfection. The expression of p53's target genes were cell line-dependent except for Mdm2 that was consistent with the findings of p53. The results of Western blotting demonstrated that the protein levels of p53 were greatly lower in UBE2Q1-transfected SW480 cells compared to the control SW480 cells. However, the reduced levels of p53 protein were not remarkable in the transfected LS180 cells compared to the control cells. The suppression of p53 is believed to be the result of UBE2Q1-dependent ubiquitination and its subsequent proteasomal degradation. Furthermore, the ubiquitination of p53 can act as a signal for degradation-independent functions, such as nuclear export and suppressing the p53's transcriptional activities. In this context, the decreased Mdm2 levels can moderate the proteasome-independent mono-ubiquitination of p53. The ubiquitinated p53 modulates the transcriptional levels of target genes. Therefore, the up-modulation of UBE2Q1 may influence the transcriptional activities depending on p53, and thereby contributes to CRC progression through regulating the p53.
Collapse
Affiliation(s)
- Maryam Rasouli
- Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Khakshournia
- Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, 71348-14336, Iran
| | - Omid Vakili
- Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, 71348-14336, Iran
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sanaz Dastghaib
- Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Atefeh Seghatoleslam
- Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sayed Mohammad Shafiee
- Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, 71348-14336, Iran.
| |
Collapse
|
|
23
|
Masdor NA, Abu Bakar MF, Hod R, Mohammed Nawi A. Green space exposure and colorectal cancer: A systematic review. Heliyon 2023; 9:e15572. [PMID: 37153430 PMCID: PMC10160744 DOI: 10.1016/j.heliyon.2023.e15572] [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: 03/21/2023] [Revised: 04/14/2023] [Accepted: 04/14/2023] [Indexed: 05/09/2023] Open
Abstract
Green space has been linked to colorectal cancer, but the evidence is still limited and inconclusive. This review aimed to investigate the relationship between green space and CRC. The studies were searched using three primary journal databases: PubMed, Scopus, and Web of Science. The retrieved citations were screened, and data from articles about GS exposure and CRC were extracted. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was used to evaluate the studies' quality. Five of the 1792 articles identified were eligible for the final review, which included five cohort studies published between 2017 and 2022. Each one article from the United States, the United Kingdom, France, Belgium, and Germany and All studies are of high quality. Four studies reported CRC incidence and one study reported CRC mortality from GS exposure. There was no significant association between GS attributes (Normalized Difference Vegetation Index (NDVI), surrounding greenness, surrounding green area, proximity to GS (agricultural lands, urban GSs, and forests), and count of recreational facilities and parks) with CRC. Only one study discovered that a healthier ecosystem was linked to a lower CRC risk. Although the evidence is still limited, the findings may indicate the presence of other factors in the relationship between GS and CRC. Future research should continue to focus on the variation of GS and the factors that influence it. Specific attention to the development of GS has the potential to produce benefits while mitigating cancer risk.
Collapse
|
|
24
|
Soleimanifar H, Mahmoodzadeh Hosseini H, Samavarchi Tehrani S, Mirhosseini SA. The Anti-Adhesion Effect of Nisin as a Robust Lantibiotic on the Colorectal Cancer Cells. Adv Biomed Res 2023; 12:113. [PMID: 37288013 PMCID: PMC10241620 DOI: 10.4103/abr.abr_267_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 05/07/2022] [Accepted: 05/09/2022] [Indexed: 06/09/2023] Open
Abstract
Background Bacteriocins are a type of antimicrobial peptide that are produced by probiotics. They have been studied as possible therapeutic drugs and have been used to suppress bacterial development in foods. Nisin is a potent bacteriocin having the anti-microbial and anti-cancer characteristics produced by Lactococcus lactis. The aim of the present paper is to evaluate the influence of Nisin on cell adhesion and its two related genes, mmp-2 and mmp-9, in the colorectal cancer cell line. Materials and Methods For this purpose, HT-29 cells were treated with various concentrations of Nisin and the cell cytotoxicity, cell adhesion, and gene expression were evaluated using the MTT assay, cell adhesion assay, and real-time PCR. Results Our findings showed that 32 to 1024 μg/ml of Nisin resulted in a significant reduction in cell viability (P < 0.05). Furthermore, 128 and 256 μg/ml of Nisin significantly reduced the cell adhesion, and mmp-2 and mmp-9 gene expressions (P < 0.05). Conclusion Our findings suggested that Nisin could prevent metastasis and cancer progression.
Collapse
Affiliation(s)
- Hesam Soleimanifar
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hamideh Mahmoodzadeh Hosseini
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Sadra Samavarchi Tehrani
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Ali Mirhosseini
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
25
|
Li C, Yu H, Zhu Z, Shang X, Huang Y, Sabanayagam C, Yang X, Liu L. Association of blood pressure with incident diabetic microvascular complications among diabetic patients: Longitudinal findings from the UK Biobank. J Glob Health 2023; 13:04027. [PMID: 36960684 PMCID: PMC10039372 DOI: 10.7189/jogh.13.04027] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2023] Open
Abstract
Background Evidence suggests a correlation of blood pressure (BP) level with presence of diabetic microvascular complications (DMCs), but the effect of BP on DMCs incidence is not well-established. We aimed to explore the associations between BP and DMCs (diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy) risk in participants with diabetes. Methods This study included 23 030 participants, free of any DMCs at baseline, from the UK Biobank. We applied multivariable-adjusted Cox regression models to estimate BP-DMCs association and constructed BP genetic risk scores (GRSs) to test their association with DMCs phenotypes. Differences in incidences of DMCs were also compared between the 2017 ACC/AHA and JNC 7 guidelines (traditional criteria) of hypertension. Results Compared to systolic blood pressure (SBP)<120 mm Hg, participants with SBP≥160 mm Hg had a hazard ratio (HR) of 1.50 (95% confidence interval (CI) = 1.09, 2.06) for DMCs. Similarly, DMCs risk increased by 9% for every 10 mm Hg of higher SBP at baseline (95% CI = 1.04, 1.13). The highest tercile SBP GRS was associated with 32% higher DMCs risk (95% CI = 1.11, 1.56) compared to the lowest tercile. We found no significant differences in DMCs incidence between JNC 7 and 2017 ACC/AHA guidelines. Conclusions Genetic and epidemiological evidence suggests participants with higher SBP had an increased risk of DMCs, but hypertension defined by 2017 ACC/AHA guidelines may not impact DMCs incidence compared with JNC 7 criteria, contributing to the care and prevention of DMCs.
Collapse
Affiliation(s)
- Cong Li
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Honghua Yu
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangzhou, China
| | - Zhuoting Zhu
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Xianwen Shang
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yu Huang
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Charumathi Sabanayagam
- Singapore Eye Research Institute (SERI) and Singapore National Eye Centre, Population Health, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- National University of Singapore, Singapore, Singapore
| | - Xiaohong Yang
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Lei Liu
- Guangdong Eye Institute, Department of ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Department of Ophthalmology, Jincheng People's Hospital, Jincheng, Shanxi Province, China
| |
Collapse
|
|
26
|
Analysis of factors associated with postoperative acute kidney injury in patients with colorectal cancer and the development of a risk prediction model: a retrospective study. Updates Surg 2023:10.1007/s13304-023-01481-z. [PMID: 36892811 DOI: 10.1007/s13304-023-01481-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 02/23/2023] [Indexed: 03/10/2023]
Abstract
BACKGROUND To investigate the factors associated with acute kidney injury (AKI) in postoperative colorectal cancer (CRC) patients and develop a risk prediction model. METHODS The clinical data of 389 CRC patients were retrospectively analyzed. The patients were divided into AKI (n = 30) and non-AKI groups (n = 359) according to KDIGO diagnostic criteria. Demographic data, the presence of underlying diseases, perioperative conditions and related examination results were compared between the two groups. Binary logistic regression was used to analyze the independent risk factors for postoperative AKI, and a risk prediction model was established. And a verification group (94 patients) was used to verify the model. RESULTS 30 patients (7.71%) with CRC had postoperative AKI. Binary logistic regression analysis showed that preoperative combined hypertension, preoperative anemia, inadequate intraoperative crystalloid infusion, low intraoperative minimum mean arterial pressure (MAP) and moderate to severe postoperative decline in hemoglobin (Hb) levels were independent risk factors. The risk prediction model developed was expressed as Logit P = - 0.853 + 1.228 * preoperative combined hypertension + 1.275 *preoperative anemia - 0.002 * intraoperative crystalloid infusion (ml) - 0.091 * intraoperative minimum MAP (mmHg) + 1.482 * moderate to severe postoperative decline in Hb levels. In Hosmer-Lemeshow test, χ2 = 8.157, P = 0.718 showed that the fitting effect was good. The area under ROC curve was 0.776 (95% CI 0.682-0.871, P < 0.001), with a prediction threshold of 1.570, a sensitivity of 63.3% and a specificity of 88.9%. The sensitivity and specificity of the verification group were 65.8% and 86.1%. CONCLUSIONS Preoperative combined hypertension, preoperative anemia, inadequate intraoperative crystalloid infusion, low intraoperative minimum MAP, and moderate to severe postoperative decline in Hb levels were independent risk factors for AKI development in CRC patients. The prediction model can effectively predict the occurrence of postoperative AKI in patients with CRC.
Collapse
|
|
27
|
Chen X, Guo F, Chang-Claude J, Hoffmeister M, Brenner H. Physical activity, polygenic risk score, and colorectal cancer risk. Cancer Med 2023; 12:4655-4666. [PMID: 35891576 PMCID: PMC9972112 DOI: 10.1002/cam4.5072] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 11/09/2022] Open
Abstract
INTRODUCTION Whether and to what extent the relationship between physical activity (PA) and colorectal cancer (CRC) differs according to CRC-related genetic risk remains to be determined, and no studies to date have quantified how much genetically determined risk could be compensated for with active exercise. METHODS Genetic risk was quantified by a polygenic risk score (PRS) summarizing the estimated effect of 140 CRC-associated genetic variants. Associations of PA with CRC risk were estimated by multivariable logistic regression across PRS levels. We also compared the impact of PA and specific PA types to the PRS using "genetic risk equivalent (GRE)", a novel approach to enhance effective risk communication. RESULTS Among 5058 CRC patients and 4134 controls, we observed no significant association between overall PA level in quartiles and CRC risk. However, the highest versus lowest lifetime leisure time physical activity (LTPA) was associated with a 13% lower CRC risk [odds ratio 0.87, 95% confidence interval (CI) 0.77-1.00] independent of PRS levels (adjusted p value for interaction = 0.18). This effect was equivalent to the effect of having 11 percentiles lower PRS (GRE -10.6, 95% CI -20.7 to -0.6). The GRE (95% CI) for the highest lifetime sports tertile was -23.0 (-33.9 to -12.0). CONCLUSIONS LTPA was inversely associated with CRC risk irrespective of polygenic risk for CRC, which reinforces the importance of LTPA in CRC prevention among the general population. Adequate sports activity can compensate for a large share of polygenic risk for CRC.
Collapse
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
| | - Feng Guo
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jenny Chang-Claude
- Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Genetic Tumor Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, 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 Consortium (DKTK), 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
| |
Collapse
|
|
28
|
Byrne S, Boyle T, Ahmed M, Lee SH, Benyamin B, Hyppönen E. Lifestyle, genetic risk and incidence of cancer: a prospective cohort study of 13 cancer types. Int J Epidemiol 2023:6990971. [PMID: 36651198 DOI: 10.1093/ije/dyac238] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 12/20/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with the risk of 13 types of cancer and whether these associations differ according to genetic risk using data from the UK Biobank. METHODS In 2006-2010, participants aged 37-73 years had their lifestyle assessed and were followed up for incident cancers until 2015-2019. Analyses were restricted to those of White European ancestry with no prior history of malignant cancer (n = 195 822). Polygenic risk scores (PRSs) were computed for 13 cancer types and these cancers combined ('overall cancer'), and a lifestyle index was calculated from WCRF recommendations. Associations with cancer incidence were estimated using Cox regression, adjusting for relevant confounders. Additive and multiplicative interactions between lifestyle index and PRSs were assessed. RESULTS There were 15 240 incident cancers during the 1 926 987 person-years of follow-up (median follow-up = 10.2 years). After adjusting for confounders, the lifestyle index was associated with a lower risk of overall cancer [hazard ratio per standard deviation increase (95% CI) = 0.89 (0.87, 0.90)] and of eight specific cancer types. There was no evidence of interactions on the multiplicative scale. There was evidence of additive interactions in risks for colorectal, breast, pancreatic, lung and bladder cancers, such that the recommended lifestyle was associated with greater change in absolute risk for persons at higher genetic risk (P < 0.0003 for all). CONCLUSIONS The recommended lifestyle has beneficial associations with most cancers. In terms of absolute risk, the protective association is greater for higher genetic risk groups for some cancers. These findings have important implications for persons most genetically predisposed to those cancers and for targeted strategies for cancer prevention.
Collapse
Affiliation(s)
- Stephanie Byrne
- Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
- UniSA Allied Health & Human Performance, University of South Australia, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Terry Boyle
- Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
- UniSA Allied Health & Human Performance, University of South Australia, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Muktar Ahmed
- Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
- Department of Epidemiology, Faculty of Public Health, Jimma University Institute of Health, Jimma, Ethiopia
| | - Sang Hong Lee
- Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
- UniSA Allied Health & Human Performance, University of South Australia, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Beben Benyamin
- Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
- UniSA Allied Health & Human Performance, University of South Australia, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
| | - Elina Hyppönen
- Australian Centre for Precision Health, University of South Australia, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute, Adelaide, SA, Australia
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia
| |
Collapse
|
|
29
|
Pourali G, Kazemi D, Pourali R, Rahmani N, Razzaghi E, Maftooh M, Fiuji H, Ghorbani E, Khazaei M, Ferns GA, Hassanian SM, Avan A. Bioactive Peptides: Potential Impact on the Treatment of Gastrointestinal Cancers. Curr Pharm Des 2023; 29:2450-2460. [PMID: 37877510 DOI: 10.2174/0113816128261378231019201709] [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: 05/10/2023] [Revised: 09/05/2023] [Accepted: 09/14/2023] [Indexed: 10/26/2023]
Abstract
We have reviewed the potential use of bioactive peptides in the treatment of gastrointestinal (GI) malignancies, which are a significant cause of morbidity and mortality globally. Conventional therapies, such as surgery, chemotherapy, and radiotherapy, are associated with numerous side effects that may lead to longterm complications. Bioactive peptides are short-chain amino acids that can be extracted from natural sources or synthesized, and they have various potential health benefits, including anti-inflammatory, anti-hypertensive, antioxidant, antimicrobial, and anti-cancer properties. Bioactive peptides can be acquired from animal or plant sources, and can be classified based on their function, such as ACE-inhibiting, antimicrobial, and electrolyte- regulating peptides. Recent studies have demonstrated the promising role of bioactive peptides in tumor suppression, especially when combined with conventional therapies. In this study, we have reviewed the beneficial properties of bioactive peptides and their role in suppressing tumor activity. The mechanisms of bioactive peptides in tumor suppression are discussed. We have further reviewed the findings of preclinical and clinical studies that have investigated the application of bioactive peptides in the treatment of GI cancers. This review highlights the potential use of bioactive peptides as a promising treatment method for GI malignancies to increase the quality of life of GI cancer patients.
Collapse
Affiliation(s)
- Ghazaleh Pourali
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Danial Kazemi
- School of Medicine, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan, Iran
| | - Roozbeh Pourali
- Student Research Committee, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Nafise Rahmani
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Erfan Razzaghi
- School of Medicine, Isfahan University of Medical Sciences, Hezar Jerib Street, Isfahan, Iran
| | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Fiuji
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elnaz Ghorbani
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, Sussex BN1 9PH, UK
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
30
|
Exposome approach for identifying modifiable factors for the prevention of colorectal cancer. Sci Rep 2022; 12:21615. [PMID: 36517625 PMCID: PMC9750985 DOI: 10.1038/s41598-022-25832-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022] Open
Abstract
Previous studies have shown certain exposure factors (such as lifestyle and metabolism) are associated with colorectal cancer (CRC) events. However, the application of the exposome theoretical frame and the extent to which the exposome domain can modulate the risk of CRC remain unknown. Our study aimed to construct valid exposome measurements and examine the relationship between exposome counts and the risk of CRC. This study included 335,370 individuals in the UK Biobank. We used exploratory factor analysis to identify a valid construct of exposome factors. We then summed the exposome counts within each domain. Cox proportional hazard models were used to estimate the hazard ratios and 95% confidence intervals of CRC risk related to the exposome factors and counts. During an 8.69 year median follow-up, 10,702 CRC cases were identified. Five domains were extracted from 12 variables, including ecosystem, lifestyle, tobacco and alcohol use, social economics, and social support. The Cox model results showed that the ecosystem was positively related to the reduced CRC risk (HR = 0.970; 95% CI 0.952-0.989). Similar results were also found among the domains of healthy lifestyles (HR = 0. 889; 95% CI 0.871-0.907), and no tobacco and alcohol use (HR = 0.892; 95% CI 0.876-0.909). The disadvantageous social economic (HR = 1.081; 95% CI 1.058-1.105) and insufficient social support domains (HR = 1.036; 95% CI 1.017-1.056) were associated with an increased risk of CRC. Similar risk trends were also observed across the exposome count groups with CRC incidence. Our findings suggest that certain exposure domains are related to the incidence of CRC. Ecosystem, lifestyle, and social factors can be incorporated into prediction models to identify individuals at high risk of CRC.
Collapse
|
|
31
|
Chen X, Ding J, Li H, Carr PR, Hoffmeister M, Brenner H. The power of a healthy lifestyle for cancer prevention: the example of colorectal cancer. Cancer Biol Med 2022; 19:j.issn.2095-3941.2022.0397. [PMID: 36476570 PMCID: PMC9724224 DOI: 10.20892/j.issn.2095-3941.2022.0397] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE We aimed to directly compare the estimated effects of adherence to a healthy lifestyle with those of risk predisposition according to known genetic variants affecting colorectal cancer (CRC) risk, to support effective risk communication for cancer prevention. METHODS A healthy lifestyle score (HLS) was derived from 5 lifestyle factors: smoking, alcohol consumption, diet, physical activity, and body adiposity. The association of lifestyle and polygenic risk score (PRS) (based on 140 CRC-associated risk loci) with CRC risk was assessed with multiple logistic regression and compared through the genetic risk equivalent (GRE), a novel approach providing an estimate of the effects of adherence to a healthy lifestyle in terms of percentile differences in PRS. RESULTS A higher HLS was associated with lower CRC risk (4,844 cases, 3,964 controls). Those adhering to all 5 healthy lifestyle factors had a 62% (95% CI 54%-68%) lower CRC risk than those adhering to ≤ 2 healthy lifestyle factors. The estimated effect of adherence to all 5 compared with ≤ 2 healthy lifestyle factors was as strong as the effect of having a 79 percentile (GRE 79, 95% CI 61-97) lower PRS. The association between a healthy lifestyle and CRC risk was independent of PRS level but was particularly pronounced among those with a family history of CRC in ≥ 1 first-degree relative (P-interaction = 0.0013). CONCLUSIONS A healthy lifestyle was strongly inversely associated with CRC risk. The large GRE indicated that CRC risk determined by polygenic risk may be offset to a substantial extent by adherence to a healthy lifestyle.
Collapse
Affiliation(s)
- Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany,Medical Faculty Heidelberg, Heidelberg University, Heidelberg 69120, Germany
| | - Jie Ding
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Hengjing Li
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany,Medical Faculty Heidelberg, Heidelberg University, Heidelberg 69120, Germany
| | - Prudence R. Carr
- School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany,Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany,Correspondence to: Hermann Brenner, E-mail:
| |
Collapse
|
|
32
|
Kadkhoda S, Ghafouri-Fard S, Noorbakhsh F, Ravaei S, Darbeheshti F, Amoli MM, Taslimi R, Shakoori A. The importance of regulatory pathway mediated by Circ0001955 in colorectal cancer. Exp Mol Pathol 2022; 128:104819. [PMID: 35914612 DOI: 10.1016/j.yexmp.2022.104819] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 04/10/2022] [Accepted: 07/22/2022] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC. METHODS After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed. RESULTS Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters. CONCLUSION Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.
Collapse
Affiliation(s)
- Sepideh Kadkhoda
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farshid Noorbakhsh
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sima Ravaei
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzaneh Darbeheshti
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mahsa M Amoli
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Taslimi
- Department of Gastroenterology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Abbas Shakoori
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Medical Genetics, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
33
|
Bi JH, Yuan HY, Jiang Y, Zhang Y, Zheng WW, Zhang L, Li ZY, Li HL, Tan YT, Zhao WS, Xiang YB. Incidence, Mortality Features and Lifetime Risk Estimation of Digestive Tract Cancers in an Urban District of Shanghai, China. J Epidemiol Glob Health 2022; 12:248-257. [PMID: 35751747 PMCID: PMC9470802 DOI: 10.1007/s44197-022-00047-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 06/05/2022] [Indexed: 10/28/2022] Open
Abstract
Digestive tract cancers are the common cause of cancer deaths in both China and worldwide. This study aimed to describe the burden, recent trends and lifetime risks in the incidence and mortality of digestive tract cancers in an urban district of Shanghai, China. Our study extracted data on stomach, colon, rectum and liver cancers diagnosed in Changning District between 2010 and 2019 from the Shanghai Cancer Registry. We calculated age-standardized incidence and mortality rates, the risks of developing and dying from cancer, and the estimated annual percent changes. Between 2010 and 2019, 8619 new cases and 5775 deaths were registered with digestive tract cancers in the district. The age-standardized incidence rates (ASIRs) of liver cancer decreased steadily, whereas the ASIRs of stomach, colon and rectum cancers remained stable from 2010 to 2019. The age-standardized mortality rates (ASMRs) of stomach and liver cancers showed significant declining changes from 2010 to 2019 in both sexes, but that of colon and rectum cancers remained stable during the entire period. The risks of developing and dying from digestive tract cancers were substantially higher in men than women. The burden of digestive tract cancer and its disparities between sex and age group remain major public health challenges in urban Shanghai. To reduce the burden of digestive tract cancers, the government and researchers should develop and promote a healthy diet, organize a screening, and reduce the prevalence of smoking, alcohol drinking, and hepatitis B virus and hepatitis C virus infections.
Collapse
Affiliation(s)
- Jing-Hao Bi
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Hui-Yun Yuan
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Yu Jiang
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Yun Zhang
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Wen-Wei Zheng
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Lei Zhang
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China
| | - Zhuo-Ying Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Hong-Lan Li
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Yu-Ting Tan
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China
| | - Wen-Sui Zhao
- Shanghai Changning District Center for Disease Control and Prevention, No. 39, Yun Wu Shan Road, Shanghai, 200051, People's Republic of China.
| | - Yong-Bing Xiang
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
- State Key Laboratory of Oncogene and Related Genes & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xie Tu Road, Shanghai, 200032, People's Republic of China.
| |
Collapse
|
|
34
|
Li J, Jiang T, Ren ZC, Wang ZL, Zhang PJ, Xiang GA. Early detection of colorectal cancer based on circular DNA and common clinical detection indicators. World J Gastrointest Surg 2022; 14:833-848. [PMID: 36157359 PMCID: PMC9453338 DOI: 10.4240/wjgs.v14.i8.833] [Citation(s) in RCA: 3] [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: 04/12/2022] [Revised: 05/14/2022] [Accepted: 08/05/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer worldwide, and it is the second leading cause of death from cancer in the world, accounting for approximately 9% of all cancer deaths. Early detection of CRC is urgently needed in clinical practice.
AIM To build a multi-parameter diagnostic model for early detection of CRC.
METHODS Total 59 colorectal polyps (CRP) groups, and 101 CRC patients (38 early-stage CRC and 63 advanced CRC) for model establishment. In addition, 30 CRP groups, and 62 CRC patients (30 early-stage CRC and 32 advanced CRC) were separately included to validate the model. 51 commonly used clinical detection indicators and the 4 extrachromosomal circular DNA markers NDUFB7, CAMK1D, PIK3CD and PSEN2 that we screened earlier. Four multi-parameter joint analysis methods: binary logistic regression analysis, discriminant analysis, classification tree and neural network to establish a multi-parameter joint diagnosis model.
RESULTS Neural network included carcinoembryonic antigen (CEA), ischemia-modified albumin (IMA), sialic acid (SA), PIK3CD and lipoprotein a (LPa) was chosen as the optimal multi-parameter combined auxiliary diagnosis model to distinguish CRP and CRC group, when it differentiated 59 CRP and 101 CRC, its overall accuracy was 90.8%, its area under the curve (AUC) was 0.959 (0.934, 0.985), and the sensitivity and specificity were 91.5% and 82.2%, respectively. After validation, when distinguishing based on 30 CRP and 62 CRC patients, the AUC was 0.965 (0.930-1.000), and its sensitivity and specificity were 66.1% and 70.0%. When distinguishing based on 30 CRP and 32 early-stage CRC patients, the AUC was 0.960 (0.916-1.000), with a sensitivity and specificity of 87.5% and 90.0%, distinguishing based on 30 CRP and 30 advanced CRC patients, the AUC was 0.970 (0.936-1.000), with a sensitivity and specificity of 96.7% and 86.7%.
CONCLUSION We built a multi-parameter neural network diagnostic model included CEA, IMA, SA, PIK3CD and LPa for early detection of CRC, compared to the conventional CEA, it showed significant improvement.
Collapse
Affiliation(s)
- Jian Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China
- Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, Guangdong Province, China
- Department of General Surgery, Henan Tumor Hospital, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Tao Jiang
- Medicine Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
| | - Zeng-Ci Ren
- Department of General Surgery, Henan Tumor Hospital, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Zhen-Lei Wang
- Department of General Surgery, Henan Tumor Hospital, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
| | - Peng-Jun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Guo-An Xiang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong Province, China
- Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, Guangdong Province, China
| |
Collapse
|
|
35
|
In silico high throughput screening and in vitro validation of a novel Raf/Mek dual inhibitor against colorectal carcinoma. Biologia (Bratisl) 2022. [DOI: 10.1007/s11756-022-01197-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
|
|
36
|
Yu J, Feng Q, Kim JH, Zhu Y. Combined Effect of Healthy Lifestyle Factors and Risks of Colorectal Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality: Systematic Review and Meta-Analysis. Front Oncol 2022; 12:827019. [PMID: 35936678 PMCID: PMC9353059 DOI: 10.3389/fonc.2022.827019] [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: 12/01/2021] [Accepted: 06/20/2022] [Indexed: 11/29/2022] Open
Abstract
Background In addition to adiposity, lifestyle factors such as poor diet, low physical activity, alcohol intake and smoking are noted to be associated with the development of colorectal cancer (CRC). This study aims to investigate the association and dose-response relationship between adherence to a healthy lifestyle and CRC risk. Methods A systematic literature search was conducted in MEDLINE and EMBASE for studies examining multiple lifestyle factors with risk of CRC, incident colorectal adenoma (CRA), and CRC-specific mortality through June 2021 without restrictions on language or study design. Meta-analysis was performed to pool hazard ratios using random-effects model. Subgroup analyses were performed based upon study and sample characteristics. Random-effects dose-response analysis was also conducted for CRC risk to assess the effect of each additional healthy lifestyle factor. Results A total of 28 studies (18 cohort studies, eight case-control studies, and two cross-sectional study) were included. When comparing subjects with the healthiest lifestyle to those with the least healthy lifestyle, the pooled HR was statistically significant for CRC (0.52, 95% CI 0.44-0.63), colon cancer (0.54, 95% CI 0.44-0.67), rectal cancer (0.51, 95% CI 0.37-0.70), CRA (0.39, 95% CI 0.29-0.53), and CRC-specific mortality (0.65, 95% CI 0.52-0.81). The pooled HR for CRC was 0.91 (95% CI: 0.88-0.94) for each increase in the number of healthy lifestyles. The inverse association between healthy lifestyle and CRC risk was consistently observed in all subgroups (HR ranging from 0.26 to 0.86). Conclusions Adoption of a higher number of healthy lifestyles is associated with lower risk of CRC, CRA, and CRC-specific mortality. Promoting healthy lifestyle could reduce the burden of CRC. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=231398, identifier CRD42021231398.
Collapse
Affiliation(s)
- Jiazhou Yu
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Qi Feng
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Jean H. Kim
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yimin Zhu
- Department of Epidemiology & Biostatistics, and Department of Respiratory Diseases of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Center, Zhejiang University, Hangzhou, China
- *Correspondence: Yimin Zhu,
| |
Collapse
|
|
37
|
Fan H, Zhang J, Zou B, He Z. The Role of CEP55 Expression in Tumor Immune Response and Prognosis of Patients with Non-small Cell lung Cancer. ARCHIVES OF IRANIAN MEDICINE 2022; 25:432-442. [PMID: 36404510 PMCID: PMC11904281 DOI: 10.34172/aim.2022.72] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 11/20/2021] [Indexed: 03/15/2025]
Abstract
BACKGROUND With the continuous advancement of diagnostic methods, more and more early-stage Non-small cell lung cancer (NSCLC) patients are diagnosed. Although many scholars have devoted substantial efforts to investigate the pathogenesis and prognosis of NSCLC, its molecular mechanism is still not well explained. METHODS We retrieved three gene datasets GSE10072, GSE19188 and GSE40791 from the Gene Expression Omnibus (GEO) database and screened and identified differentially expressed genes (DEGs). Then, we performed KEGG and GO functional enrichment analysis, survival analysis, risk analysis and prognosis analysis on the selected hub genes. We constructed a protein-protein interaction (PPI) network, and used the STRING database and Cytoscape software. RESULTS The biological process analysis showed that these genes were mainly enriched in cell division and nuclear division. Survival analysis showed that the genes of CEP55 (centrosomal protein 55), NMU (neuromedin U), CAV1 (Caveolin 1), TBX3 (T-box transcription factor 3), FBLN1 (fibulin 1) and SYNM (synemin) may be involved in the development, invasion or metastasis of NSCLC (P<0.05, logFC>1). Prognostic analysis and independent prognostic analysis showed that the expression of these hub gene-related mRNAs was related to the prognostic risk of NSCLC. Risk analysis showed that the selected hub genes were closely related to the overall survival time of patients with NSCLC. CONCLUSION The DEGs and hub genes screened and identified in this study will help us to understand the molecular mechanisms of NSCLC, and CEP55 expression affects the survival and prognosis of patients with NSCLC, and participates in tumor immune response.
Collapse
Affiliation(s)
- Haiyin Fan
- Thoracic Department, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
| | - Jin Zhang
- Ultrasound Department, Jiangxi Chest Hospital, Nanchang, Jiangxi, China
| | - Bin Zou
- Thoracic Department, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
| | - Zhisheng He
- Thoracic Department, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China
| |
Collapse
|
|
38
|
da Silva RC, Fagundes RR, Faber KN, Campos ÉG. Pro-Oxidant and Cytotoxic Effects of Tucum-Do-Cerrado ( Bactris setosa Mart.) Extracts in Colorectal Adenocarcinoma Caco-2 Cells. Nutr Cancer 2022; 74:3723-3734. [PMID: 35703849 DOI: 10.1080/01635581.2022.2086704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Colorectal cancer is one of the most common types of cancer. Bioactive natural compounds can act in cancer chemoprevention as tumor growth inhibitors. Tucum-do-cerrado (Bactris setosa Mart.) is a Brazilian fruit that contains several phenolic compounds. This study investigated the effect of tucum aqueous extract in Caco-2 cells in comparison to primary human intestinal organoids and fibroblasts. Cells were exposed to 0.5 and 1 mg/ml of tucum aqueous extract for 24 h. ROS production, mRNA levels for SOD1 and SOD2, CAT, GPX1, NFE2L2, HIF1A and NOS2 were evaluated in Caco-2 cells exposed to tucum extract. Cell viability of Caco-2 cells was decreased upon tucum extract exposure. Mitochondrial ROS levels increased in Caco-2 cells exposed to tucum extract. The mRNA levels of SOD1, SOD2, CAT, GPX, NFE2L2 and HIF1A were downregulated in Caco-2 cells exposed to tucum extract, while NOS2 mRNA levels remained unchanged. Protein levels of SOD2, CAT and NRF2 remained unchanged in Caco-2 cells treated with tucum extract, indicating that catalase and SOD2 cellular functions may be unaffected by the tucum extract at 24 h, of exposure. Aqueous extract of tucum-do-cerrado may induce cellular toxicity in a cancer cell-specific manner, possibly through increased mitochondrial ROS production and gene expression regulation.
Collapse
Affiliation(s)
- Renata Cristina da Silva
- Programa de Pós-Graduação em Nutrição Humana, Laboratório de Biologia Molecular, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brazil.,Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Raphael Rosa Fagundes
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Élida Geralda Campos
- Programa de Pós-Graduação em Nutrição Humana, Laboratório de Biologia Molecular, Departamento de Biologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brazil
| |
Collapse
|
|
39
|
Lin J, Chen H, Huang Y, Tang W, Zhang S, Chen Y. Lack of Association Between PDCD-1 Polymorphisms and Colorectal Cancer Risk: A Case-Control Study. Immunol Invest 2022; 51:1867-1882. [PMID: 35499255 DOI: 10.1080/08820139.2022.2069504] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Functional variants of immune-related genes may be implicated in the occurrence of colorectal cancer (CRC). In this study, Programmed cell death (PDCD)-1.6 (rs10204525 T/C), PDCD-1.7 (rs7421861 A/G), and PDCD-1.9 (rs2227982 A/G) loci were selected to explore gene expression and the potential susceptibility to the development of CRC. Here, 1,003 CRC patients and 1,303 controls were included and three PDCD-1 tagging loci were selected and analyzed by using SNPscan genotyping assays. SHESIS software was harnessed to obtain the haplotypes of the PDCD-1 gene. We found that the genotype and allele distribution of PDCD-1 tagging loci did not significantly affect the risk of CRC. Adjustment for body mass index, age, smoking, alcohol using and sex also found that PDCD-1 tagging loci did not influence the occurrence of CRC. In conclusion, this study suggests that the PDCD-1 tagging loci (rs10204525, rs7421861, and rs2227982) are not correlated with CRC susceptibility.
Collapse
Affiliation(s)
- Jing Lin
- Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, Fujian, China.,Center, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalCancer Bio-Immunotherapy, Fuzhou, Fujian, China
| | - Hanshen Chen
- Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yufang Huang
- Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, Fujian, China.,Center, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalCancer Bio-Immunotherapy, Fuzhou, Fujian, China
| | - Weifeng Tang
- Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Sheng Zhang
- Department of General Surgery, Changzhou Third People's Hospital, Changzhou, Jiangsu, China
| | - Yu Chen
- Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou, Fujian, China.,Center, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalCancer Bio-Immunotherapy, Fuzhou, Fujian, China.,College of Chemistry, Fuzhou University, Fuzhou, China
| |
Collapse
|
|
40
|
Syed Soffian SS, Mohammed Nawi A, Hod R, Ja’afar MH, Isa ZM, Chan HK, Hassan MRA. Meta-Analysis of the Association between Dietary Inflammatory Index (DII) and Colorectal Cancer. Nutrients 2022; 14:nu14081555. [PMID: 35458117 PMCID: PMC9031004 DOI: 10.3390/nu14081555] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 04/03/2022] [Accepted: 04/05/2022] [Indexed: 02/07/2023] Open
Abstract
The Dietary Inflammatory Index (DII) was extensively used to examine the inflammatory potential of diet related to colorectal cancer (CRC). This meta-analysis aimed to update the evidence of the association between the DII and CRC across various culture-specific dietary patterns. Literature search was performed through online databases (Scopus, Web of Science, PubMed, and EBSCOHost). Observational studies exploring the association between the DII and CRC, published between 2017 and 2021, were included. The risk ratio (RR) and 95% confidence interval (CI) were separately computed for 12 studies comparing the highest and lowest DII scores and for 3 studies that presented continuous DII scores. A high DII score was associated with a higher risk of CRC (RR:1.16; 95% CI, 1.05–1.27). In the subgroup analysis, significant associations were seen in cohort design (RR: 1.24; 95% CI, 1.06–1.44), those lasting for 10 years or longer (RR: 2.95; 95% CI, 2.47–3.52), and in adjustment factor for physical activity (RR: 1.13; 95% CI, 1.07–1.20). An increase of one point in the DII score elevates the risk of CRC by 1.34 (95% CI: 1.15–1.55) times. The findings call for standardized measurement of the inflammatory potential of diet in future studies to enable the establishment of global guidelines for CRC prevention.
Collapse
Affiliation(s)
- Sharifah Saffinas Syed Soffian
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (S.S.S.S.); (R.H.); (M.H.J.); (Z.M.I.)
| | - Azmawati Mohammed Nawi
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (S.S.S.S.); (R.H.); (M.H.J.); (Z.M.I.)
- Correspondence:
| | - Rozita Hod
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (S.S.S.S.); (R.H.); (M.H.J.); (Z.M.I.)
| | - Mohd Hasni Ja’afar
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (S.S.S.S.); (R.H.); (M.H.J.); (Z.M.I.)
| | - Zaleha Md Isa
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (S.S.S.S.); (R.H.); (M.H.J.); (Z.M.I.)
| | - Huan-Keat Chan
- Clinical Research Center, Sultanah Bahiyah Hospital, Alor Setar 05400, Malaysia; (H.-K.C.); (M.R.A.H.)
| | - Muhammad Radzi Abu Hassan
- Clinical Research Center, Sultanah Bahiyah Hospital, Alor Setar 05400, Malaysia; (H.-K.C.); (M.R.A.H.)
| |
Collapse
|
|
41
|
Sassano M, Mariani M, Quaranta G, Pastorino R, Boccia S. Polygenic risk prediction models for colorectal cancer: a systematic review. BMC Cancer 2022; 22:65. [PMID: 35030997 PMCID: PMC8760647 DOI: 10.1186/s12885-021-09143-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 12/02/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. METHODS We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. RESULTS We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. CONCLUSIONS Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.
Collapse
Affiliation(s)
- Michele Sassano
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168, Roma, Italy
| | - Marco Mariani
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168, Roma, Italy
| | - Gianluigi Quaranta
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168, Roma, Italy
- Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| | - Roberta Pastorino
- Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
| | - Stefania Boccia
- Section of Hygiene, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168, Roma, Italy
- Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
| |
Collapse
|
|
42
|
Chen Q, Fan Y, Li Y, Wang J, Chen L, Lin J, Chen F, Wang J, Qiu Y, Shi B, Pan L, Lin L, He B, Liu F. A novel nutritional risk score and prognosis of oral cancer patients: A prospective study. Oral Dis 2022; 28:108-115. [PMID: 33237576 DOI: 10.1111/odi.13733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 11/05/2020] [Accepted: 11/17/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVES To evaluate the prognostic performance of a novel nutritional risk score based on serum iron, hemoglobin, and body mass index (BMI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS X-tile analysis was performed to determine the optimal cutoff values of serum iron, hemoglobin, and BMI. A nutritional risk score was established by using the HR values of serum iron, hemoglobin, and BMI. Kaplan-Meier curve and multivariable Cox proportional hazards models were used to evaluate the prognostic value of the nutritional risk score in overall survival (OS) and oral cancer-specific survival (OCSS). RESULTS Serum iron, hemoglobin, and body mass index were all inversely related to the prognosis of oral cancer. The adjusted HR of serum iron, hemoglobin, and BMI were 1.562, 1.886, and 1.465 for OS, and 1.653, 1.865, and 1.443 for OCSS. Patients with higher nutritional risk score had a poorer OS and OCSS. Additionally, chemotherapy was only associated with improved OCSS in patients with the lowest nutritional risk score, but not in patients with higher one. CONCLUSIONS Nutritional risk score is of prognostic value in oral cancer patients. Favorable response to chemotherapy may only be observed in well-nourished oral cancer patients with lower nutritional risk score.
Collapse
Affiliation(s)
- Qing Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Yi Fan
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Yanni Li
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Jing Wang
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Lin Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Jing Lin
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Fa Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Jing Wang
- Laboratory Center, The Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fujian, China
| | - Yu Qiu
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Bin Shi
- Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Fujian Medical University, Fujian, China
| | - Lizhen Pan
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Lisong Lin
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Baochang He
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| | - Fengqiong Liu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fujian, China
| |
Collapse
|
|
43
|
Anisman H, Kusnecov AW. Dietary components associated with being overweight, having obesity, and cancer. Cancer 2022. [DOI: 10.1016/b978-0-323-91904-3.00018-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
|
|
44
|
Ghrouz I, El Sharif N. Diet and Genetic Risk Factors of Colorectal Cancer in Palestine: A Case-Control Study. Nutr Cancer 2021; 74:2460-2469. [PMID: 34875940 DOI: 10.1080/01635581.2021.2013507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
To add evidence to the limited data available on colorectal cancer (CRC) from Palestine, we examine the risk factors associated with CRC using a matched hospital-based case-control study. A structured questionnaire was used to collect data from 105 cases and 105 controls. A multivariable conditional regression model was used to adjust for the association between study factors and CRC risk. In the model, compared with controls, cases from villages were significantly less likely to have CRC (Adjusted Odds Ratio, AOR = 0.194); taking aspirin lowered the likelihood of CRC by 24%; and having a multiple birth sibling by 33%. Also, the likelihood of CRC was lowered significantly by consuming five servings of fruits/vegetables per week or more (5-6 servings: AOR = 0.21, 7-8 servings per week: AOR = 0.04). However, cases had a significantly higher likelihood of CRC if they consumed 2-4 servings of grilled red meat per week (AOR = 4.25); smoked (AOR = 4.38); had a sedentary lifestyle (AOR = 2.53); reported parental consanguinity (AOR = 3.88); or had a family history of cancer (AOR = 6.39). Our results confirmed the association between CRC and red meat intake and smoking, and proved that parental consanguinity and family history of cancer are also risk factors for CRC.
Collapse
Affiliation(s)
- Issa Ghrouz
- Faculty of Public Health, Al Quds University, Abu Dis Campus, Jerusalem, Palestine
| | - Nuha El Sharif
- Faculty of Public Health, Al Quds University, Abu Dis Campus, Jerusalem, Palestine
| |
Collapse
|
|
45
|
Yang J, Zhao L, Zhang N, Du Z, Li Y, Li X, Zhao D, Wang J. Cancer death and potential years of life lost in Feicheng City, China: Trends from 2013 to 2018. Medicine (Baltimore) 2021; 100:e27370. [PMID: 34596152 PMCID: PMC8483870 DOI: 10.1097/md.0000000000027370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 08/29/2021] [Accepted: 09/13/2021] [Indexed: 01/05/2023] Open
Abstract
ABSTRACT This study aimed to evaluate the impact of cancer-related mortality on life expectancy in Feicheng City.We extracted the death records and population data of Feicheng City from 2013 to 2018 through the Feicheng Center for Disease Control and Prevention. The mortality, premature mortality, cause-eliminated life expectancy, potential years of life lost (PYLL), average potential years of life lost (APYLL), annual change percentage (APC), and other indicators of cancer were calculated. The age-standardized rates were calculated using the sixth national census (2010).From 2013 to 2018, the mortality rate of cancer in Feicheng City was 221.55/100,000, and the standardized mortality rate was 166.37/100,000. The standardized mortality rate increased from 2013 to 2014 and then decreased annually. The premature mortality of cancer was 8.98% and showed a downward trend (APC = -2.47%, t = -3.10, P = .04). From 2013 to 2018, the average life expectancy of residents in Feicheng City was 78.63 years. Eliminating the impact of cancer, life expectancy could increase by 3.72 years. The rate of life loss caused by cancer in men was higher than that in women. The total life loss caused by cancer deaths was 126,870.50 person-years, the potential life loss rate was 22.51‰, and the average potential life loss was 13.30 years. The standardized potential years of life lost rate showed a downward trend (APC = -2.96%, t = -3.72, P = .02), and APYLL decreased by 1.98% annually (t = -5.44, P = .01). The top 5 malignant tumors in APYLL were leukemia, breast cancer, brain tumor, liver cancer, and ovarian cancer.Lung cancer, esophageal cancer, female breast cancer, and childhood leukemia have a great impact on the life expectancy of residents in Feicheng City. Effective measures need to be taken to reduce the disease burden of malignant tumors.
Collapse
Affiliation(s)
- Jia Yang
- Liaocheng People's Hospital, Liaocheng, Shandong, China
| | - Li Zhao
- Cancer Prevention and Trentment Center, Feicheng People's Hospital, Feicheng, Shandong, China
| | - Nan Zhang
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zhenhua Du
- Feicheng Center for Disease Control and Prevention, Feicheng, Shandong, China
| | - Yanyan Li
- Cancer Prevention and Trentment Center, Feicheng People's Hospital, Feicheng, Shandong, China
| | - Xia Li
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China
| | - Deli Zhao
- Cancer Prevention and Trentment Center, Feicheng People's Hospital, Feicheng, Shandong, China
| | - Jialin Wang
- Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| |
Collapse
|
|
46
|
Niu M, Zhang L, Wang Y, Tu R, Liu X, Wang C, Bie R. Lifestyle Score and Genetic Factors With Hypertension and Blood Pressure Among Adults in Rural China. Front Public Health 2021; 9:687174. [PMID: 34485217 PMCID: PMC8416040 DOI: 10.3389/fpubh.2021.687174] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/21/2021] [Indexed: 12/20/2022] Open
Abstract
Background: Although high genetic risk and unhealthful lifestyles are associated with a high risk of hypertension, but the combined relationship between lifestyle score and genetic factors on blood pressure remains limited, especially in resource-constrained areas. Aim: To explore the separate and joint effects between genetic and lifestyle factors on blood pressure and hypertension in rural areas. Methods: In 4,592 adults from rural China with a 3-year of follow-up, a genetic risk score (GRS) was established using 13 single nucleotide polymorphisms (SNPs) and the lifestyle score was calculated including factors diet, body mass index (BMI), smoking status, drinking status, and physical activity. The associations of genetic and lifestyle factors with blood pressure and hypertension were determined with generalized linear and logistic regression models, respectively. Results: The high-risk GRS was found to be associated with evaluated blood pressure and hypertension and the healthful lifestyle with diastolic blood pressure (DBP) level. Individuals with unhealthful lifestyles in the high GRS risk group had an odds ratio (OR) (95% CI) of 1.904 (1.006, 3.603) for hypertension than those with a healthful lifestyle in the low GRS risk group. Besides, the relative risk (RR), attributable risk (AR), and population attributable risk (PAR) for unhealthful lifestyle are 1.39, 5.87, 0.04%, respectively, and the prevented fraction for the population (PFP) for healthful lifestyle is 9.47%. Conclusion: These results propose a joint effect between genetic and lifestyle factors on blood pressure and hypertension. The findings provide support for adherence to a healthful lifestyle in hypertension precision prevention. Clinical Trial Registration: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx?proj=11375.
Collapse
Affiliation(s)
- Miaomiao Niu
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Liying Zhang
- School of Information Engineering, Zhengzhou University, Zhengzhou, China
| | - Yikang Wang
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Runqi Tu
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiaotian Liu
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Chongjian Wang
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Ronghai Bie
- Department of Preventive Medicine, Henan University of Chinese Medicine, Zhengzhou, China
| |
Collapse
|
|
47
|
Kadkhoda S, Taslimi R, Noorbakhsh F, Darbeheshti F, Bazzaz JT, Ghafouri-Fard S, Shakoori A. Importance of Circ0009910 in colorectal cancer pathogenesis as a possible regulator of miR-145 and PEAK1. World J Surg Oncol 2021; 19:265. [PMID: 34479583 PMCID: PMC8417957 DOI: 10.1186/s12957-021-02378-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 08/26/2021] [Indexed: 02/08/2023] Open
Abstract
Introduction Colorectal cancer (CRC) is one of the most frequent neoplasms in the world. Based on the emerging role of noncoding RNAs, particularly circular RNAs in pathogenesis of cancers, we designed this study to inspect the expression levels of a circ0009910-mediated regulatory pathway in colorectal cancer. Methods After bioinformatics analyses and construction of putative circ0009910/ miR-145-5p/PEAK1 pathway, the expression levels of these components were evaluated in 50 CRC tissues and adjacent specimens by quantitative real-time PCR. Moreover, we appraised the correlation coefficients between these transcripts and calculated the correlation between circ0009910 expression levels with clinicopathological features of patients. Results Circ0009910 and PEAK1 were significantly upregulated, while miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0009910, miR-145-5p, and PEAK1. We also reported considerable correlations between circ0009910 expression and clinicopathological parameters including sex and perineural invasion. Finally, ROC curve analysis showed circ0009910 level as a discriminative biomarker for CRC. Conclusion For the first time, we could introduce circ0009910 as an important biomarker in CRC. Collectively, this investigation helped us to identify a newly diagnosed pathway in CRC that can be a potential axis for designing effective drugs for treatment of CRC patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02378-0.
Collapse
Affiliation(s)
- Sepideh Kadkhoda
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Taslimi
- Department of Gastroenterology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshid Noorbakhsh
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzaneh Darbeheshti
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Javad Tavakkoly Bazzaz
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Abbas Shakoori
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. .,Department of Medical Genetics, Cancer Institute of Iran, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Dr. Qarib St., Keshavarz Blvd, Tehran, Iran.
| |
Collapse
|
|
48
|
Martínez-Casillas KCE, Saucedo-Sariñana AM, Barros-Núñez P, Gallegos-Arreola MP, Pineda-Razo TD, Marín-Contreras ME, Flores-Martínez SE, Rosales-Reynoso MA. MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2021; 24:1033-1040. [PMID: 34804420 PMCID: PMC8591758 DOI: 10.22038/ijbms.2021.56874.12690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 07/05/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVES The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in several processes like inflammation, apoptosis, and tumorigenesis. Several authors have proposed that genetic variations in these genes may alter their expression with subsequent cancer risk. This study aimed to examine the possible association of MKK4 rs3826392 and rs3809728 variants in Mexican patients with colorectal cancer (CRC). These variants were also compared with clinical features as sex, age, TNM stage, and tumor location. MATERIALS AND METHODS The study included genomic DNA from 218 control subjects and 250 patients. Genotyping of the MKK4 variants was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. RESULTS Individuals with A/T and T/T genotypes for the rs3809728 (-1044 A>T) variant showed a significantly increased risk for CRC (P=0.012 and 0.007, respectively); while individuals with the G/G genotype for the rs3826392 (-1304 T>G) variant showed a decreased risk for CRC (P=0.012). Genotypes of the MKK4 rs3809728 variant were also significantly related to colon localization and advanced TNM stage in CRC patients. T-T haplotype (rs3826392 and rs3809728) of the MKK4 gene was associated with risk in patients with CRC. CONCLUSION The rs3826392 variant in the MKK4 gene could be a cancer protective factor, while the rs3809728 variant could be a risk factor. These variants play a significant role in CRC risk.
Collapse
Affiliation(s)
| | - Anilú Margarita Saucedo-Sariñana
- División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
| | - Patricio Barros-Núñez
- Unidad de Investigación Seguimiento Enfermedades Metabólicas, Unidad Médica de Alta Especialidad Pediatría, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco. México
| | - Martha Patricia Gallegos-Arreola
- División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
| | - Tomás Daniel Pineda-Razo
- Servicio de Oncología Médica, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
| | - María Eugenia Marín-Contreras
- Servicio de Gastroenterología, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
| | - Silvia Esperanza Flores-Martínez
- División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México
| | - Mónica Alejandra Rosales-Reynoso
- División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México,Corresponding author: Mónica Alejandra Rosales-Reynoso. División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México. Tel/ Fax: +52-3336683000;
| |
Collapse
|
|
49
|
Rubín-García M, Martín V, Vitelli-Storelli F, Moreno V, Aragonés N, Ardanaz E, Alonso-Molero J, Jiménez-Moleón JJ, Amiano P, Fernández-Tardón G, Molina-Barceló A, Alguacil J, Dolores-Chirlaque M, Álvarez-Álvarez L, Pérez-Gómez B, Dierssen-Sotos T, Olmedo-Requena R, Guevara M, Fernández-Villa T, Pollán M, Benavente Y. [Family history of first degree as a risk factor for colorectal cancer]. GACETA SANITARIA 2021; 36:345-352. [PMID: 34272081 DOI: 10.1016/j.gaceta.2021.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 04/12/2021] [Accepted: 04/23/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To evaluate the association between first-degree family history and colorectal cancer (CRC). METHOD We analyzed data from 2857 controls and 1360 CRC cases, collected in the MCC-Spain project. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of association with the family history of CRC was estimated by non-conditional logistic regression. RESULTS First-degree relatives doubled the risk of CRC (OR: 2.19; 95% CI: 1.80-2.66), increasing in those with two or more (OR: 4.22; 95% CI: 2.29-7.78) and in those whose relatives were diagnosed before 50 years (OR: 3.24; 95% CI: 1.52-6.91). Regarding the association of the family history with the location, no significant differences were observed between colon and rectum, but there were in the relation of these with the age of diagnosis, having more relatives those diagnosed before 50 years (OR: 4.79; 95% CI: 2.65-8.65). CONCLUSIONS First-degree relatives of CRC increase the chances of developing this tumor, they also increase when the relative is diagnosed at an early age. Therefore, it must be a target population on which to carry out prevention measures.
Collapse
Affiliation(s)
- María Rubín-García
- Grupo de Investigación en Interacciones Gen-Ambiente y Salud, Instituto de Biomedicina (IBIOMED), Universidad de León, León, España
| | - Vicente Martín
- Grupo de Investigación en Interacciones Gen-Ambiente y Salud, Instituto de Biomedicina (IBIOMED), Universidad de León, León, España; CIBER de Epidemiología y Salud Pública (CIBERESP), España.
| | - Facundo Vitelli-Storelli
- Grupo de Investigación en Interacciones Gen-Ambiente y Salud, Instituto de Biomedicina (IBIOMED), Universidad de León, León, España
| | - Víctor Moreno
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Departamento de Ciencias Clínicas, Facultad de Medicina, Universidad de Barcelona, Barcelona, España; Programa de Analítica de Datos Oncológicos (PADO), Instituto Catalán de Oncología (ICO), L'Hospitalet del Llobregat, Barcelona, España; Programa ONCOBELL, Instituto de Investigación Biomédica de Bellvitge Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, España
| | - Nuria Aragonés
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Dirección General de Salud Pública, Madrid, España
| | - Eva Ardanaz
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Instituto de Salud Pública y Laboral de Navarra, Pamplona, España; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, España
| | - Jéssica Alonso-Molero
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Universidad de Cantabria - IDIVAL, Santander, España
| | - José J Jiménez-Moleón
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, España; Departamento de Medicina Preventiva y Salud Pública. Universidad de Granada, España
| | - Pilar Amiano
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Departamento de Salud del Gobierno Vasco, Subdirección de Salud Pública y Adicciones de Gipuzkoa, San Sebastián, España; Instituto de Investigaciones Sanitarias Biodonostia, Grupo de Epidemiología de Enfermedades Crónicas y Transmisibles, San Sebastián, España
| | - Guillermo Fernández-Tardón
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), IUOPA, Universidad de Oviedo, Asturias, España
| | | | - Juan Alguacil
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Centro de Investigación en Recursos Naturales, Salud y Medio Ambiente (RENSMA), Universidad de Huelva, Campus Universitario de El Carmen, Huelva, España
| | - María Dolores-Chirlaque
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Departamento de Epidemiología, Consejería de Salud, IMIB-Arrixaca, Universidad de Murcia, El Palmar, Murcia, España
| | - Laura Álvarez-Álvarez
- Grupo de Investigación en Interacciones Gen-Ambiente y Salud, Instituto de Biomedicina (IBIOMED), Universidad de León, León, España
| | - Beatriz Pérez-Gómez
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Unidad de Cáncer y Epidemiología Ambiental, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, España; Grupo de Investigación en Epidemiología del Cáncer, Área de Oncología y Hematología, IIS Puerta de Hierro, Madrid, España
| | - Trinidad Dierssen-Sotos
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Universidad de Cantabria - IDIVAL, Santander, España
| | - Rocío Olmedo-Requena
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Instituto de Investigación Biosanitaria (ibs.GRANADA), Granada, España; Departamento de Medicina Preventiva y Salud Pública. Universidad de Granada, España
| | - Marcela Guevara
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Instituto de Salud Pública y Laboral de Navarra, Pamplona, España; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, España
| | - Tania Fernández-Villa
- Grupo de Investigación en Interacciones Gen-Ambiente y Salud, Instituto de Biomedicina (IBIOMED), Universidad de León, León, España
| | - Marina Pollán
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Unidad de Cáncer y Epidemiología Ambiental, Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, España
| | - Yolanda Benavente
- CIBER de Epidemiología y Salud Pública (CIBERESP), España; Programa de Recerca en Epidemiologia del Càncer, Institut Català d'Oncologia (IDIBELL), L'Hospitalet de Llobregat, Barcelona, España
| |
Collapse
|
|
50
|
Jin H, Pang L, Li H, Xu M, Yan H, Li R. [Value of combined detection of ITGA4 and SFRP2 gene methylation in stool DNA in diagnosis and prognostic evaluation of colorectal tumors]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:891-897. [PMID: 34238742 DOI: 10.12122/j.issn.1673-4254.2021.06.12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the value of quantitative detection of ITGA4 and SFRP2 gene methylation in stool DNA for the early diagnosis and prognostic evaluation of colorectal tumors. OBJECTIVE Real-time PCR was used for quantitative assessment of ITGA4 and SFRP2 gene methylation levels in stool samples of 85 patients with colorectal cancer, 65 patients with colorectal adenoma and 40 healthy subjects. OBJECTIVE The 3 groups were comparable for age and gender composition. Methylated ITGA4 and SFRP2 promoters were detected in 48.2% and 62.4% of patients with colorectal cancer, respectively, with a combined positivity of 81.2%. ITGA4 and SFRP2 promoter methylation was detected in 23.1% and 43.1% of patients with colorectal adenoma, respectively, with a combined positivity of 69.2%. The positivity rates of ITGA4 and SFRP2 methylation were significantly higher in patients with colorectal cancer than in those with colorectal adenoma (P < 0.001; P= 0.001) and healthy subjects (P < 0.001; P < 0.001). In colorectal cancer group, ITGA4 and SFRP2 promoter methylation levels were correlated with postoperative tumor recurrence in colorectal cancer group, and the relapse-free survival rate was significantly lower in positive patients for ITGA4 and SFRP2 promoter methylation than in the negative patients (P=0.0002; P=0.007). Multivariate analysis with the COX proportional hazard regression model showed that methylation of ITGA4 and SFRP2 gene promoters (P=0.01) and the degree of tumor differentiation (P=0.03) were associated with the recurrence of colorectal cancer, and were independent risk factors for the recurrence of colorectal cancer. OBJECTIVE Combined detection of ITGA4 and SFRP2 gene methylation levels in stool DNA can improve the early diagnosis rate of colorectal tumor. ITGA4 and SFRP2 promoter methylation and the degree of tumor differentiation are independent risk factors for colorectal cancer recurrence.
Collapse
Affiliation(s)
- H Jin
- Department of Clinical Laboratory, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang 157011, China
| | - L Pang
- First School of Clinical Medicine, Mudanjiang Medical University, Mudanjiang 157011, China
| | - H Li
- Department of Quality Control, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang 157011, China
| | - M Xu
- Department of Clinical Laboratory, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang 157011, China
| | - H Yan
- Department of Clinical Laboratory, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang 157011, China
| | - R Li
- Department of Clinical Laboratory, Affiliated Hongqi Hospital, Mudanjiang Medical University, Mudanjiang 157011, China
| |
Collapse
|