Dietary intake of folate and alcohol, MTHFR C677T polymorphism, and colorectal cancer risk in Korea.

BACKGROUND The incidence of colorectal cancer (CRC) is increasing sharply in Korea, and evidence has suggested the role of dietary methyl supply and related polymorphisms on colorectal carcinogenesis. OBJECTIVE We investigated the association between folate and alcohol intake, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and CRC risk in Koreans. DESIGN A total of 787 cases and 656 controls were recruited from 2 university hospitals. Multiple logistic regression models were used to estimate ORs and corresponding 95% CIs. RESULTS MTHFR 677T homozygotes were at a lower risk of CRC (OR: 0.60; 95% CI: 0.46, 0.78 for TT compared with CC/CT). High folate intake was associated with reduced CRC risk (OR: 0.64; 95% CI: 0.49, 0.84 for high compared with low intake), and high alcohol consumption was associated with increased risk of CRC (OR: 1.76; 95% CI: 1.26, 2.46 for high compared with low intake). When data were stratified by the amount of dietary methyl (combined intake of folate and alcohol), those with low-methyl diets had higher risk of CRC (OR: 2.32; 95% CI: 1.18, 4.56) than did those with high-methyl diets among CC/CT carriers, whereas the amount of dietary methyl did not affect the CRC risk among carriers with the TT homozygous variant. This association was stronger in patients with colon cancer than in patients with rectal cancer. CONCLUSION We found that the effect of dietary methyl supply on colorectal carcinogenesis may differ according to MTHFR C677T genotype and the subsite of origin in a Korean population.

[1]  J. Mason,et al.  Folate and carcinogenesis: an integrated scheme. , 2000, The Journal of nutrition.

[2]  K. Matsuo,et al.  Alcohol drinking and colorectal cancer in Japanese: a pooled analysis of results from five cohort studies. , 2008, American journal of epidemiology.

[3]  R. Waterland.  Assessing the effects of high methionine intake on DNA methylation. , 2006, The Journal of nutrition.

[4]  Y. Kakeji,et al.  Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: The Fukuoka Colorectal Cancer Study , 2004, Cancer science.

[5]  C. Ulrich,et al.  Colorectal adenomas and the C677T MTHFR polymorphism: evidence for gene-environment interaction? , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[6]  C. Mathers,et al.  Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 , 2010, International journal of cancer.

[7]  L. Marchand,et al.  Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. , 2009, American journal of epidemiology.

[8]  Elizabeth L. Barry,et al.  Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. , 2007, JAMA.

[9]  B. Shane.  Folate fortification: enough already? , 2003, The American journal of clinical nutrition.

[10]  C. Ulrich,et al.  Folate Supplementation: Too Much of a Good Thing? , 2006, Cancer Epidemiology Biomarkers & Prevention.

[11]  P. Radice,et al.  Different Genetic Features Associated with Colon and Rectal Carcinogenesis , 2004, Clinical Cancer Research.

[12]  A. Roddam,et al.  Folate intake and colorectal cancer risk: A meta‐analytical approach , 2005, International journal of cancer.

[13]  C. Ulrich.  Folate and Cancer Prevention—Where to Next? Counterpoint , 2008, Cancer Epidemiology Biomarkers & Prevention.

[14]  S. Shaw,et al.  Cleavage of folates during ethanol metabolism. Role of acetaldehyde/xanthine oxidase-generated superoxide. , 1989, The Biochemical journal.

[15]  M. Lai,et al.  Colorectal cancer, one entity or three , 2009, Journal of Zhejiang University SCIENCE B.

[16]  M. Singer,et al.  Nutritional Epidemiology , 2020, Definitions.

[17]  C. Ulrich,et al.  Folate and cancer--timing is everything. , 2007, JAMA.

[18]  K. Matsuo,et al.  One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan. , 2005, Carcinogenesis.

[19]  W. Leung,et al.  Increasing incidence of colorectal cancer in Asia: implications for screening. , 2005, The Lancet. Oncology.

[20]  E. Riboli,et al.  Alcohol intake and colorectal cancer risk: A dose–response meta‐analysis of published cohort studies , 2007, International journal of cancer.

[21]  W. Willett,et al.  Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer , 2010, Cancer Causes & Control.

[22]  B. Henderson,et al.  The MTHFR C677T Polymorphism and Colorectal Cancer: The Multiethnic Cohort Study , 2005, Cancer Epidemiology Biomarkers & Prevention.

[23]  Sang-Woon Choi,et al.  Folate status: effects on pathways of colorectal carcinogenesis. , 2002, The Journal of nutrition.

[24]  F. Stickel,et al.  Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism , 2010, Genes & Nutrition.

[25]  N. Brockton.  Localized depletion: the key to colorectal cancer risk mediated by MTHFR genotype and folate? , 2006, Cancer Causes & Control.

[26]  L. Kolonel,et al.  B-vitamin intake, metabolic genes, and colorectal cancer risk (United States) , 2002, Cancer Causes & Control.

[27]  M. Salaspuro,et al.  Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency , 2000, International journal of cancer.

[28]  J. Little,et al.  Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. , 2004, American journal of epidemiology.

[29]  B. Schneider.  MANUAL of the international statistical classification of diseases, injuries, and causes of death. Addendum 1. Supplementary interpretations and instructions for coding causes of death. , 1953, Bulletin of the World Health Organization. Supplement.

[30]  M. Inoue,et al.  Calibration of a food frequency questionnaire in Koreans. , 2003, Asia Pacific journal of clinical nutrition.

[31]  D. Girelli,et al.  A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  E. Giovannucci.  Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies. , 2004, The Journal of nutrition.

[33]  Young-In Kim.  Folate and colorectal cancer: an evidence-based critical review. , 2007, Molecular nutrition & food research.

[34]  J. Manson,et al.  Folate, vitamin B6, multivitamin supplements, and colorectal cancer risk in women. , 2006, American journal of epidemiology.

[35]  M. Ryan-Harshman,et al.  Diet and colorectal cancer: Review of the evidence. , 2007, Canadian family physician Medecin de famille canadien.

[36]  E. Rimm,et al.  A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. , 1996, Cancer research.

[37]  C. Ulrich,et al.  Does Folic Acid Supplementation Prevent or Promote Colorectal Cancer? Results from Model-Based Predictions , 2008, Cancer Epidemiology Biomarkers & Prevention.

[38]  E. Riboli,et al.  Low folate levels may protect against colorectal cancer , 2006, Gut.

[39]  W. Willett,et al.  Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. , 1997, Cancer research.

[40]  E. Rimm,et al.  Methylenetetrahydrofolate reductase, alcohol dehydrogenase, diet, and risk of colorectal adenomas. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[41]  F. Nagengast,et al.  Dietary Intake of Folate and Riboflavin, MTHFR C677T Genotype, and Colorectal Adenoma Risk: A Dutch Case-Control Study , 2005, Cancer Epidemiology Biomarkers & Prevention.

[42]  M. Inoue,et al.  Development of a food frequency questionnaire in Koreans. , 2003, Asia Pacific journal of clinical nutrition.

[43]  W. Willett,et al.  Comparison of risk factors for colon and rectal cancer , 2004, International journal of cancer.

[44]  S. Kono,et al.  Methylenetetrahydrofolate reductase polymorphism, alcohol intake, and risks of colon and rectal cancers in Korea. , 2004, Cancer letters.

[45]  Sang-Woon Choi,et al.  Effects of alcohol on folate metabolism: implications for carcinogenesis. , 2005, Alcohol.

[46]  W. Willett,et al.  Alcohol Intake and Colorectal Cancer: A Pooled Analysis of 8 Cohort Studies , 2004, Annals of Internal Medicine.

[47]  Y. Coyle,et al.  Lifestyle, genes, and cancer. , 2009, Methods in molecular biology.

[48]  A. Tjønneland,et al.  Micronutrient intake and risk of colon and rectal cancer in a Danish cohort. , 2010, Cancer epidemiology.

[49]  F. Stickel,et al.  Alcohol Consumption and Cancer of the Gastrointestinal Tract , 2006, Digestive Diseases.