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Zhang X, Xu Z, Shang L, Yang Q, Ye H, Liu H, Zou Y, Lu Y, Zheng Z, Li M, Wang P, Zhu J. Global burden of colorectal cancer attributable to metabolic risks from 1990 to 2021, with predictions to 2046. BMC Cancer 2025; 25:228. [PMID: 39930395 PMCID: PMC11809015 DOI: 10.1186/s12885-025-13643-w] [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: 10/10/2024] [Accepted: 02/04/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Metabolic risks are significant factors associated with colorectal cancer. This study aimed to assess global, regional and national burden for CRC attributable to metabolic risks from 1990 to 2021 and to predict mortality by 2046. METHODS Data from the Global Burden of Disease Study 2021 were used to quantify deaths, disability-adjusted life years (DALYs), and age-standardized rates of CRC due to metabolic risk factors, disaggregated by sex, age, region, country/territory, and sociodemographic index (SDI). The average annual percentage change (AAPC) was used to analyze temporal trends from 1990 to 2021. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Future mortality trends up to 2046 were forecast using age-period-cohort models. RESULTS Globally, CRC deaths attributable to metabolic risks increased 2.47-fold, rising from 73,443 in 1990 to 181,689 in 2021. The global age-standardized mortality rates (ASMRs) and age-standardized rates of DALYs (ASDRs) of CRC attributable to high FPG and ASDRs attributable to high BMI increased from 1990 to 2021. The ASMRs and ASDRs of males was higher than that of females, with increasing trends. Central Europe had the highest ASMRs and ASDRs of CRC attributable to metabolic risks in 2021. Most regions and countries showed increasing trends in ASMR and ASDR for CRC due to metabolic risks, with Andean Latin America, Southeast Asia, and Cabo Verde increasing the most. High-SDI regions had the largest burden of CRC attributable to metabolic risks, while burden of other SDI regions have been significantly increased. A positive association was observed between SDI and age-standardized rates (ASMR: RFPG = 0.803, RBMI = 0.752; ASDR: RFPG = 0.812, RBMI = 0.756). By 2046, the ASMR of CRC attributable to high FPG was projected to remain stable and the ASMR due to high BMI was expected to see a slightly increase. CONCLUSION Colorectal cancer deaths and DALYs attributable to metabolic risk factors remain high, particularly in males and high-SDI regions. Further researches into the metabolic mechanisms of CRC and effective treatment strategies are needed.
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Affiliation(s)
- Xiaoyue Zhang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
| | - Ziqing Xu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Lin Shang
- Department of Science and Technology of Henan Province, Zhengzhou, Henan Province, 450008, China
| | - Qian Yang
- Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University/Maternal and Child Health Hospital of Henan Province, Zhengzhou, Henan Province, 450052, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Haiyan Liu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Yuanlin Zou
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Yin Lu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Zhong Zheng
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Meng Li
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China.
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
| | - Jicun Zhu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
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Ungvari Z, Fekete M, Fekete JT, Grosso G, Ungvari A, Győrffy B. Adherence to the Mediterranean diet and its protective effects against colorectal cancer: a meta-analysis of 26 studies with 2,217,404 participants. GeroScience 2025; 47:1105-1121. [PMID: 39090501 PMCID: PMC11872821 DOI: 10.1007/s11357-024-01296-9] [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: 06/11/2024] [Accepted: 07/20/2024] [Indexed: 08/04/2024] Open
Abstract
Colorectal cancer (CRC) is a major global health concern and represents a significant public health challenge in Hungary, where it exhibits some of the highest morbidity and mortality rates in the European Union. The Mediterranean diet has been suggested to reduce the incidence of CRC, but comprehensive evidence from diverse study designs is needed to substantiate this effect. A systematic literature search was conducted in PubMed, ClinicalTrials.gov, CENTRAL, and the Web of Science to identify randomized controlled trials and human clinical trials from 2008 to 2024 to identify relevant studies. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HRs). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 15 clinical trials and 9 case-control studies, encompassing a total of 2,217,404 subjects. The pooled analysis indicated that adherence to the Mediterranean diet significantly reduced the prevalence of CRC (HR = 0.84, 95% CI = 0.78-0.91, p < 0.01). This protective effect was consistent across sexes, with HRs of 0.85 (95% CI = 0.75-0.97, p = 0.01) for males and 0.88 (95% CI = 0.79-0.99, p = 0.03) for females. Case-control studies specifically showed a substantial effect (HR = 0.51, 95% CI = 0.38-0.68, p < 0.01). Notable heterogeneity was observed across studies, yet the a priori information size was substantially below the cumulative sample size, ensuring sufficient data for reliable conclusions. The findings from this meta-analysis reinforce the protective role of the Mediterranean diet against CRC. The results of this meta-analysis will inform dietary interventions designed to mitigate CRC risk, which are conducted within the framework of the Semmelweis Study, an ongoing comprehensive cohort study at Semmelweis University, designed to explore the multifaceted causes of unhealthy aging in Hungary. These interventions aim to explore the practical application of Mediterranean dietary patterns in reducing CRC incidence among the Hungarian population.
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Affiliation(s)
- Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
| | - Mónika Fekete
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - János Tibor Fekete
- Department of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117, Budapest, Hungary
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
- Center for Human Nutrition and Mediterranean Foods (NUTREA), University of Catania, Catania, Italy
| | - Anna Ungvari
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary.
| | - Balázs Győrffy
- Department of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117, Budapest, Hungary
- Department of Biophysics, Medical School, University of Pecs, H-7624, Pecs, Hungary
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Zhang S, Liu L, Li S, Sun X. Effect and imaging analysis of cetuximab combined with radiotherapy in patients with rectal carcinoma. Biotechnol Genet Eng Rev 2024; 40:4953-4963. [PMID: 37248703 DOI: 10.1080/02648725.2023.2219944] [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: 02/23/2023] [Accepted: 05/23/2023] [Indexed: 05/31/2023]
Abstract
OBJECTIVE To analyze the effect of cetuximab combined with radiotherapy in patients with rectal carcinoma (RC) by imaging analysis. METHODS The clinical data of 104 RC patients at our hospital from February 2021 to February 2022 were retrospectively analyzed. They were separated into control group (n = 52) and experimental group (n = 52) according to the order of admission, with the former treated with radiotherapy alone and the latter receiving cetuximab and radiotherapy. The clinical efficacy, tumor marker levels and imaging parameters of different treatment regimens were compared, and Quality of Life questionnaire (QLQ-C30) was used to evaluate the quality of life. RESULTS The incidence of tumor regression grade (TRG) downgrade, T stage downgrade and N stage downgrade was remarkably higher in the experimental group than in the control group (P < 0.05). The experimental group had remarkably lower tumor marker levels (P < 0.001) and higher mean score of EORTC Core QLQ-C30 (P < 0.001) than those in the control group. The relative signal intensity of tumor (SIT/M), relative signal intensity reduction rate of tumor (SIT/MRR) and apparent diffusion coefficient (ADC) values were remarkably higher (P < 0.001) and the absolute signal intensity of tumor (SIT) value was remarkably lower (P < 0.001) in the experimental group than the control group. CONCLUSION Treatment with cetuximab and radiotherapy can greatly reduce serum tumor marker levels in RC patients and bring them health benefits, and further studies will help establish a better solution for such patients.
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Affiliation(s)
- Shuai Zhang
- Gastrointestinal Cancer Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China
| | - Liangliang Liu
- Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei, China
| | - Shuguang Li
- Gastrointestinal Cancer Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China
| | - Xin Sun
- Department of Imaging, The Fourth People's Hospital of Jinan, Jinan, Shandong, China
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Prabhakaran R, Thamarai R, Sivasamy S, Dhandayuthapani S, Batra J, Kamaraj C, Karthik K, Shah MA, Mallik S. Epigenetic frontiers: miRNAs, long non-coding RNAs and nanomaterials are pioneering to cancer therapy. Epigenetics Chromatin 2024; 17:31. [PMID: 39415281 PMCID: PMC11484394 DOI: 10.1186/s13072-024-00554-6] [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: 07/23/2024] [Accepted: 09/25/2024] [Indexed: 10/18/2024] Open
Abstract
Cancer has arisen from both genetic mutations and epigenetic changes, making epigenetics a crucial area of research for innovative cancer prevention and treatment strategies. This dual perspective has propelled epigenetics into the forefront of cancer research. This review highlights the important roles of DNA methylation, histone modifications and non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs, which are key regulators of cancer-related gene expression. It explores the potential of epigenetic-based therapies to revolutionize patient outcomes by selectively modulating specific epigenetic markers involved in tumorigenesis. The review examines promising epigenetic biomarkers for early cancer detection and prognosis. It also highlights recent progress in oligonucleotide-based therapies, including antisense oligonucleotides (ASOs) and antimiRs, to precisely modulate epigenetic processes. Furthermore, the concept of epigenetic editing is discussed, providing insight into the future role of precision medicine for cancer patients. The integration of nanomedicine into cancer therapy has been explored and offers innovative approaches to improve therapeutic efficacy. This comprehensive review of recent advances in epigenetic-based cancer therapy seeks to advance the field of precision oncology, ultimately culminating in improved patient outcomes in the fight against cancer.
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Affiliation(s)
- Rajkumar Prabhakaran
- Central Research Facility, Santosh Deemed to be University, Ghaziabad, UP, India
| | - Rajkumar Thamarai
- UGC Dr. D.S. Kothari Postdoctoral Fellow, Department of Animal Science, Manonmaniam Sundaranar University, Tirunelveli, Tamil Nadu, 627012, India
| | - Sivabalan Sivasamy
- Central Research Facility, Santosh Deemed to be University, Ghaziabad, UP, India
| | | | - Jyoti Batra
- Central Research Facility, Santosh Deemed to be University, Ghaziabad, UP, India.
| | - Chinnaperumal Kamaraj
- Interdisciplinary Institute of Indian System of Medicine, Directorate of Research, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India.
| | - Krishnasamy Karthik
- Department of Mechanical Engineering, Vel Tech Rangarajan Dr. Sagunthala R&D Institute of Science and Technology, Chennai, India
| | - Mohd Asif Shah
- Department of Economics, Kardan University, Parwane Du, 1001, Kabul, Afghanistan.
- Division of Research and Development, Lovely Professional University, Phagwara, Punjab, 144001, India.
- Centre of Research Impact and Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, 140401, India.
| | - Saurav Mallik
- Department of Environmental Health, Harvard T H Chan School of Public Health, Boston, Massachusetts, 02115, United States.
- Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ, 85721, USA.
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5
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Ungvari Z, Fekete M, Varga P, Lehoczki A, Fekete JT, Ungvari A, Győrffy B. Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk. GeroScience 2024:10.1007/s11357-024-01375-x. [PMID: 39379738 DOI: 10.1007/s11357-024-01375-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 10/01/2024] [Indexed: 10/10/2024] Open
Abstract
The incidence of colorectal cancer (CRC) has been steadily rising, and obesity has been identified as a significant risk factor. Numerous studies suggest a strong correlation between excess body weight and increased risk of CRC, but comprehensive quantification through pooled analysis remains limited. This study aims to systematically review and meta-analyze the existing literature to evaluate the association between obesity and CRC risk, considering variations across sex and study designs. A systematic literature search was conducted in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to identify randomized controlled trials and human clinical trials from 1992 to 2024. Statistical analysis was performed using the https://metaanalysisonline.com web application using a random effects model to estimate the pooled hazard rates (HR). Forest plots, funnel plots, and Z-score plots were utilized to visualize results. We identified 52 clinical trials and 14 case-control studies, encompassing a total of 83,251,050 and 236,877 subjects, respectively. The pooled analysis indicated that obesity significantly increased the prevalence of CRC (HR = 1.36, 95% CI = 1.24-1.48, p < 0.01). This effect was consistent across sexes, with HRs of 1.57 (95% CI = 1.38-1.78, p = 0.01) for males and 1.25 (95% CI = 1.14-1.38, p < 0.01) for females. Case-control studies specifically showed an effect, but with marginal significance only (HR = 1.27, 95% CI = 0.98-1.65, p = 0.07). The Z-score plot indicated the need for additional analysis in the case-control group. A significant heterogeneity was observed across studies in all four settings. This meta-analysis provides robust evidence that obesity is a significant risk factor for colorectal cancer, with an overall hazard rate indicating a 36% increased risk. The effect is pronounced across both sexes, with males showing a slightly higher risk compared to females. Although case-control studies showed a weaker association, the overall trend supports the link between obesity and CRC. These results underscore the importance of public health interventions aimed at reducing obesity to potentially lower the risk of colorectal cancer.
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Affiliation(s)
- Zoltan Ungvari
- Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
- Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary
| | - Mónika Fekete
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - Peter Varga
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - Andrea Lehoczki
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary
| | - János Tibor Fekete
- Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary
| | - Anna Ungvari
- Institute of Preventive Medicine and Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary.
| | - Balázs Győrffy
- Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary
- Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary
- Dept. of Biophysics, Medical School, University of Pecs, 7624, Pecs, Hungary
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Kagawa Y, Smith JJ, Fokas E, Watanabe J, Cercek A, Greten FR, Bando H, Shi Q, Garcia-Aguilar J, Romesser PB, Horvat N, Sanoff H, Hall W, Kato T, Rödel C, Dasari A, Yoshino T. Future direction of total neoadjuvant therapy for locally advanced rectal cancer. Nat Rev Gastroenterol Hepatol 2024; 21:444-455. [PMID: 38485756 PMCID: PMC11588332 DOI: 10.1038/s41575-024-00900-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/26/2024] [Indexed: 05/31/2024]
Abstract
Despite therapeutic advancements, disease-free survival and overall survival of patients with locally advanced rectal cancer have not improved in most trials as a result of distant metastases. For treatment decision-making, both long-term oncologic outcomes and impact on quality-of-life indices should be considered (for example, bowel function). Total neoadjuvant therapy (TNT), comprised of chemotherapy and radiotherapy or chemoradiotherapy, is now a standard treatment approach in patients with features of high-risk disease to prevent local recurrence and distant metastases. In selected patients who have a clinical complete response, subsequent surgery might be avoided through non-operative management, but patients who do not respond to TNT have a poor prognosis. Refined molecular characterization might help to predict which patients would benefit from TNT and non-operative management. Specifically, integrated analysis of spatiotemporal multi-omics using artificial intelligence and machine learning is promising. Three prospective trials of TNT and non-operative management in Japan, the USA and Germany are collaborating to better understand drivers of response to TNT. Here, we address the future direction for TNT.
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Affiliation(s)
- Yoshinori Kagawa
- Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan
| | - J Joshua Smith
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Emmanouil Fokas
- Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Frankfurt Cancer Institute, Frankfurt, Germany
- Department of Radiation Oncology, CyberKnife and Radiation Therapy, Centre for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
- German Cancer Consortium (DKTK), Frankfurt, Germany
| | - Jun Watanabe
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Andrea Cercek
- Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Florian R Greten
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Frankfurt Cancer Institute, Frankfurt, Germany
- German Cancer Consortium (DKTK), Frankfurt, Germany
- Institute for Tumour Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt, Germany
| | - Hideaki Bando
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Qian Shi
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Colorectal Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Paul B Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hanna Sanoff
- Department of Medicine, Division of Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - William Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Takeshi Kato
- Department of Surgery, NHO Osaka National Hospital, Osaka, Japan
| | - Claus Rödel
- Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Frankfurt Cancer Institute, Frankfurt, Germany
- German Cancer Consortium (DKTK), Frankfurt, Germany
| | - Arvind Dasari
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Takayuki Yoshino
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
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Liu G, Li CM, Xie F, Li QL, Liao LY, Jiang WJ, Li XP, Lu GM. Colorectal cancer's burden attributable to a diet high in processed meat in the Belt and Road Initiative countries. World J Gastrointest Oncol 2024; 16:182-196. [PMID: 38292848 PMCID: PMC10824120 DOI: 10.4251/wjgo.v16.i1.182] [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: 10/01/2023] [Revised: 10/20/2023] [Accepted: 12/11/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) plays a significant role in morbidity, mortality, and economic cost in the Belt and Road Initiative ("B and R") countries. In addition, these countries have a substantial consumption of processed meat. However, the burden and trend of CRC in relation to the consumption of a diet high in processed meat (DHPM-CRC) in these "B and R" countries remain unknown. AIM To analyze the burden and trend of DHPM-CRC in the "B and R" countries from 1990 to 2019. METHODS We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC. Numbers and age-standardized rates (ASRs) of deaths along with the disability-adjusted life years (DALYs) were determined among the "B and R" countries in 1990 and 2019. Using joinpoint regression analysis, the average annual percent change (AAPC) was used to analyze the temporal trends of age-standardized DALYs rate (ASDALR) from 1990 to 2019 and in the final decade (2010-2019). RESULTS We found geographical differences in the burden of DHPM-CRC among "B and R" countries, with the three highest-ranking countries being the Russian Federation, China, and Ukraine in 1990, and China, the Russian Federation, and Poland in 2019. The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019 (all P < 0.05). The absolute number of deaths and DALYs in DHPM-CRC were 3151.15 [95% uncertainty interval (UI) 665.74-5696.64] and 83249.31 (95%UI 15628.64-151956.31) in China in 2019. However, the number of deaths (2627.57-2528.51) and DALYs (65867.39-55378.65) for DHPM-CRC in the Russian Federation has declined. The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam, Southeast Asia, with an AAPC value of 3.90% [95% confidence interval (CI): 3.63%-4.16%], whereas the fastest decline was observed in Kyrgyzstan, Central Asia, with an AAPC value of -2.05% (95% CI: -2.37% to -1.73%). A substantial upward trend in ASR of mortality, years lived with disability, years of life lost, and DALYs from DHPM-CRC changes in 1990-2019 and the final decade (2010-2019) for most Maritime Silk Route members in East Asia, South Asia, Southeast Asia, North Africa, and the Middle East, as well as Central Europe, while those of the most Land Silk Route members in Central Asia and Eastern Europe have decreased markedly (all P < 0.05). The ASDALR for DHPM-CRC increased more in males than in females (all P < 0.05). For those aged 50-74 years, the ASDALR for DHPM-CRC in 40 members exhibited an increasing trend, except for 20 members, including 7 members in Central Asia, Maldives, and 12 high or high-middle social development index (SDI) members in other regions (all P < 0.05). CONCLUSION The burden of DHPM-CRC varies substantially across "B and R" countries and threatens public health. Relevant evidence-based policies and interventions tailored to the different trends of countries in SDIs or Silk Routes should be adopted to reduce the future burden of CRC in "B and R" countries via extensive collaboration.
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Affiliation(s)
- Gu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
- Department of Gastrointestinal Surgery, Chenzhou Third People’s Hospital, Chenzhou 423000, Hunan Province, China
| | - Chang-Min Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
- Department of Gastrointestinal Surgery, Chenzhou First People’s Hospital and the First Affiliated Hospital of Xiangnan University, Chenzhou, 423000 Hunan Province, China
| | - Fei Xie
- Department of Gastrointestinal Surgery, Chenzhou Third People’s Hospital, Chenzhou 423000, Hunan Province, China
| | - Qi-Lai Li
- Department of Gastrointestinal Surgery, Chenzhou Third People’s Hospital, Chenzhou 423000, Hunan Province, China
| | - Liang-Yan Liao
- Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Wen-Jun Jiang
- Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Pan Li
- Department of Health Management Center, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China
| | - Guan-Ming Lu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
- Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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Ajithkumar P, Vasantharajan SS, Pattison S, McCall JL, Rodger EJ, Chatterjee A. Exploring Potential Epigenetic Biomarkers for Colorectal Cancer Metastasis. Int J Mol Sci 2024; 25:874. [PMID: 38255946 PMCID: PMC10815915 DOI: 10.3390/ijms25020874] [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: 11/30/2023] [Revised: 01/08/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
Metastatic progression is a complex, multistep process and the leading cause of cancer mortality. There is growing evidence that emphasises the significance of epigenetic modification, specifically DNA methylation and histone modifications, in influencing colorectal (CRC) metastasis. Epigenetic modifications influence the expression of genes involved in various cellular processes, including the pathways associated with metastasis. These modifications could contribute to metastatic progression by enhancing oncogenes and silencing tumour suppressor genes. Moreover, specific epigenetic alterations enable cancer cells to acquire invasive and metastatic characteristics by altering cell adhesion, migration, and invasion-related pathways. Exploring the involvement of DNA methylation and histone modification is crucial for identifying biomarkers that impact cancer prediction for metastasis in CRC. This review provides a summary of the potential epigenetic biomarkers associated with metastasis in CRC, particularly DNA methylation and histone modifications, and examines the pathways associated with these biomarkers.
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Affiliation(s)
- Priyadarshana Ajithkumar
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand; (P.A.)
| | - Sai Shyam Vasantharajan
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand; (P.A.)
| | - Sharon Pattison
- Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand
| | - John L. McCall
- Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand
| | - Euan J. Rodger
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand; (P.A.)
| | - Aniruddha Chatterjee
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand; (P.A.)
- School of Health Sciences and Technology, UPES University, Dehradun 248007, India
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Alsakarneh S, Jaber F, Beran A, Aldiabat M, Abboud Y, Hassan N, Abdallah M, Abdelfattah T, Numan L, Clarkston W, Bilal M, Shaukat A. The National Burden of Colorectal Cancer in the United States from 1990 to 2019. Cancers (Basel) 2024; 16:205. [PMID: 38201632 PMCID: PMC10778178 DOI: 10.3390/cancers16010205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 12/23/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
CRC accounts for approximately a tenth of all cancer cases and deaths in the US. Due to large differences in demographics among the different states, we aim to determine trends in the CRC epidemiology and across different states, age groups, and genders. CRC rates, age-adjusted to the standard US population, were obtained from the GBD 2019 database. Time trends were estimated as annual percentage change (APC). A pairwise comparison was conducted between age- and gender-specific trends using the tests of parallelism and coincidence. Age-specific trends were also assessed in two age subgroups: younger adults aged 15-49 years and older adults aged 50-74 years. We also analyzed the prevalence, incidence, mortality, and DALYs in the US between 1990 and 2019. A total of 5.53 million patients were diagnosed with CRC in the US between 1990 and 2019. Overall, CRC incidence rates have significantly increased in younger adults (11.1 per 100,000 persons) and decreased in older adults (136.8 per 100,000 persons) (AAPC = 1.2 vs. -0.6; AAPC difference = 1.8, p < 0.001). Age-specific trends were neither identical (p < 0.001) nor parallel (p < 0.001), suggesting that CRC incidence rates are different and increasing at a greater rate in younger adults compared to older adults. However, for both men and women (49.4 and 35.2 per 100,000 persons), incidence rates have decreased over the past three decades at the same rate (AAPC = -0.5 vs. -0.5; AAPC difference = 0, p = 0.1). Geographically, the southern states had the highest mortality rates with Mississippi having the highest rate of 20.1 cases per 100,000 population in 2019. Massachusetts, New York, and the District of Colombia had the greatest decreases in mortality over the study period (-42.1%, -41.4%, and -40.9%). Decreased mortality was found in all states except Mississippi, where the mortality of CRC increased over the study period (+1.5%). This research provides crucial insights for policymakers to tailor resource allocation, emphasizing the dynamic nature of CRC burden across states and age groups, ultimately informing targeted strategies for prevention and intervention.
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Affiliation(s)
- Saqr Alsakarneh
- Department of Internal Medicine, University of Missouri, Kansas City, MO 64110, USA; (F.J.); (N.H.)
| | - Fouad Jaber
- Department of Internal Medicine, University of Missouri, Kansas City, MO 64110, USA; (F.J.); (N.H.)
| | - Azizullah Beran
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;
| | - Mohammad Aldiabat
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA;
| | - Yazan Abboud
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newark, NJ 07013, USA;
| | - Noor Hassan
- Department of Internal Medicine, University of Missouri, Kansas City, MO 64110, USA; (F.J.); (N.H.)
| | - Mohamed Abdallah
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA;
| | - Thaer Abdelfattah
- Division of Gastroenterology and Hepatology, Allegheny Health Network, Pittsburgh, PA 15212, USA;
| | - Laith Numan
- Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO 63103, USA;
| | - Wendell Clarkston
- Division of Gastroenterology and Hepatology, University of Missouri, Kansas City, MO 64110, USA;
| | - Mohammad Bilal
- Division of Gastroenterology and Hepatology, Minneapolis Veterans Affairs Health Care System, Minneapolis, MN 55417, USA;
| | - Aasma Shaukat
- Division of Gastroenterology, Department of Medicine and Population Health, Grossman School of Medicine, New York University, New York, NY 10003, USA;
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Tufail M. HOTAIR in colorectal cancer: structure, function, and therapeutic potential. Med Oncol 2023; 40:259. [PMID: 37530984 DOI: 10.1007/s12032-023-02131-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 07/19/2023] [Indexed: 08/03/2023]
Abstract
lncRNAs play a vital part in cancer development by regulating gene expression. Among these, the lncRNA HOTAIR has gained considerable attention due to its entanglement in multiple cellular processes, including chromatin remodeling and gene regulation. HOTAIR has a complex structure consisting of multiple domains that interact with various protein complexes and RNA molecules. In colorectal cancer (CRC), HOTAIR expression is upregulated, and its overexpression has been correlated with poor patient prognosis and resistance to chemotherapy. HOTAIR has been found to regulate gene expression and promote cancer growth by interacting with specific miRNAs. In addition, HOTAIR has been implicated in the development of treatment resistance in colorectal cancer. To develop effective treatments, it's important to understand how HOTAIR regulates gene expression. This article discusses HOTAIR's structure, functions, and mechanisms in CRC and its potential as a target for therapy. The author also suggests future research directions to better understand HOTAIR's role in CRC progression and drug resistance.
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Affiliation(s)
- Muhammad Tufail
- Institute of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
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He J, He M, Tang JH, Wang XH. Anastomotic leak risk factors following colon cancer resection: a systematic review and meta-analysis. Langenbecks Arch Surg 2023; 408:252. [PMID: 37386211 DOI: 10.1007/s00423-023-02989-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 06/16/2023] [Indexed: 07/01/2023]
Abstract
BACKGROUND Despite improved surgical techniques, anastomotic leakage is still a serious complication that can occur after colon cancer resection, resulting in increased morbidity and mortality. The aim of this study was to evaluate the risk factors for anastomotic leakage after colon cancer surgery, provide a theoretical basis for reducing its occurrence, and guide the practice of clinicians. METHODS A systematic review of PubMed, Ovid, Web of Science and Cochrane Central Register of Controlled Trials databases was conducted by using a combination of subject terms and free words for online searches. The databases were searched from their inception to 31 March 2022, and all cross-sectional, cohort or case‒control studies examining the risk factors for the development of anastomotic fistula after surgery for colon cancer were identified. RESULT A total of 2133 articles were searched for this study, and 16 publications were ultimately included, all of which were cohort studies. A total of 115,462 subjects were included, and a total of 3959 cases of anastomotic leakage occurred postoperatively, with an incidence of 3.4%. The odds ratio (OR) and 95% confidence interval (CI) were used for evaluation. Male sex (OR = 1.37, 95% CI: 1.29-1.46, P < 0.00001), BMI (OR = 1.04, 95% CI: 1.00-1.08, P = 0.03), diabetes (OR = 2.80, 95% CI: 1.81-4.33, P < 0.00001), combined lung disease (OR = 1.28, 95% CI: 1.15-1.42, P < 0.00001), anaesthesia ASA score (OR = 1.35, 95% CI: 1.24-1.46, P < 0.00001), ASA class ≥ III (OR = 1.34, 95% CI: 1.22-1.47, P < 0.00001), emergency surgery (OR = 1.31, 95% CI: 1.11-1.55, P = 0.001), open surgery (OR = 1.94, 95% CI: 1.69-2.24, P < 0.00001) and type of surgical resection (OR = 1.34, 95% CI: 1.12-1.61, P = 0.002) are risk factors for anastomotic leakage after colon cancer surgery. There is still a lack of strong evidence on whether age (OR = 1.00, 95% CI: 0.99-1.01, P = 0.36) and cardiovascular disease (OR = 1.18, 95% CI: 0.94-1.47, P = 0.16) are factors influencing the occurrence of anastomotic leakage after colon cancer surgery. CONCLUSIONS Male sex, BMI, obesity, coexisting pulmonary disease, anaesthesia ASA score, emergency surgery, open surgery and type of resection were risk factors for anastomotic leakage after colon cancer surgery. The effect of age and cardiovascular disease on postoperative anastomotic leakage in patients with colon cancer needs further study.
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Affiliation(s)
- Juan He
- College of Nursing, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China
| | - Mei He
- Dean's Office, Mianyang Central Hospital, Mianyang, Sichuan, People's Republic of China.
| | - Ji-Hong Tang
- College of Nursing, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China
| | - Xian-Hua Wang
- College of Nursing, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China
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Spatial and temporal patterns of colorectal cancer in Asia, 1990-2019. Int J Clin Oncol 2023; 28:255-267. [PMID: 36520255 DOI: 10.1007/s10147-022-02274-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Asia accounts for the largest burden of colorectal cancer (CRC) worldwide. This study examines the temporal patterns of CRC in Asia in the last three decades. METHODS The data pertaining to CRC burden measured by incidence, mortality, and disability-adjusted-life-years (DALYs) and its risk factors for 49 countries in the Asian continent were drawn from the Global Burden of Disease 2019 study between 1990 and 2019. Mortality-to-incidence ratio (MIR) was employed as a proxy indicator of 5-year survival rates. RESULTS In Asia, incident cases more than tripled from 270,851 to 1.1 million, deaths tripled from 183,252 to 560,426, and DALYs more than doubled from 5 million to 13.4 million between 1990 and 2019. The age-standardized incidence rate (ASIR) increased from 14.0/100,000 to 23.9/100,000, age-standardized mortality rate (ASMR) increased from 10.1/100,000 to 12.5/100,000, and MIR decreased from 0.68 to 0.50 between 1990 and 2019. ASIR varied 10-folds across countries from 5.6/100,000 in Bangladesh to 62.0/100,000 in Taiwan in 2019 and ASMR from 4.9/1000 in Bangladesh to 30.3/100,000 in Brunei. In 2019, diet low in milk (18.7%) and whole grains (15.2%) and calcium (16.6%) were the major contributory risk factors in CRC DALYs in 2019. CONCLUSION CRC is a fast-rising neoplasm in Asia and its burden can be curtailed by focusing on primary prevention (e.g., diet and physical activity) and secondary prevention through screening. The policy focus and resources must be directed towards capacity building, including cancer infrastructure and quality data availability from cancer registries.
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Gu WJ, Pei JP, Lyu J, Akimoto N, Haruki K, Ogino S, Zhang CD. The Burden of Early-Onset Colorectal Cancer and Its Risk Factors from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Cancers (Basel) 2022; 14:3502. [PMID: 35884567 PMCID: PMC9323588 DOI: 10.3390/cancers14143502] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/11/2022] [Accepted: 07/13/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The incidence of early-onset colorectal cancer (CRC) diagnosed before age 50 has been increasing over the past decades. Hence, we examined the global, regional, and national burden of early-onset CRC and its risk factors from 1990 to 2019. METHODS Using data from the Global Burden of Disease (GBD) Study 2019, we reported the incidence, deaths, and disability-adjusted life-years (DALYs) attributable to the risk factors of early-onset CRC. All estimates were reported with 95% uncertainty intervals (UIs). RESULTS The global numbers of early-onset CRC for incidence, deaths, and DALYs in 2019 were 225,736 (95% UI, 207,658 to 246,756), 86,545 (80,162 to 93,431), and 4,259,922 (3,942,849 to 4,590,979), respectively. Despite large variations at the regional and national levels, the global incidence rate, death rate, and DALY rate increased from 1990 to 2019. Diets low in milk, diets low in calcium, and alcohol use were the leading risk factors in 2019. From 1990 to 2019, a high body mass index and high fasting plasma glucose ranked remarkably higher among males and females, while smoking and diets low in fiber ranked lower among both sexes, with a more profound change among females. CONCLUSIONS Despite large variations in regional and national levels, the global incidence rate, death rate, and DALY rate increased during the past three decades. These findings may provide policymakers with an accurate quantification of the burden of early-onset CRC and targeted identification of those most at risk to mitigate the burden of early-onset CRC.
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Affiliation(s)
- Wan-Jie Gu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; (W.-J.G.); (J.L.)
| | - Jun-Peng Pei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, China;
| | - Jun Lyu
- Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; (W.-J.G.); (J.L.)
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (N.A.); (K.H.); (S.O.)
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (N.A.); (K.H.); (S.O.)
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA; (N.A.); (K.H.); (S.O.)
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02115, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA 02115, USA
| | - Chun-Dong Zhang
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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