Methylenetetrahydrofolate Reductase, Diet, and Risk of Colon Cancer

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 1999-06, Vol.8 (6), p.513-518
• Main Authors: SLATTERY, M. L, POTTER, J. D, SAMOWITZ, W, SCHAFFER, D, LEPPERT, M
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alcohol Drinking - adverse effects; Biological and medical sciences; California - epidemiology; Case-Control Studies; Colonic Neoplasms - epidemiology; Colonic Neoplasms - etiology; Colonic Neoplasms - prevention & control; Diet; Diet Surveys; DNA Methylation; Female; Folic Acid - administration & dosage; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Homozygote; Humans; Incidence; Male; Medical sciences; Methionine - administration & dosage; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation - genetics; Oxidoreductases Acting on CH-NH Group Donors - genetics; Pyridoxine - administration & dosage; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Vitamin B 12 - administration & dosage
• ISSN: 1055-9965; 1538-7755

Individuals with different forms of the 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene, carriers of the C677T mutation versus wild type, show differences in enzyme levels; these differences have been hypothesized to be related to DNA methylation and, perhaps, to the nucleotide pool size. Using data from an incident case-control study, we evaluated the combined effect of dietary intake of folate, methionine, vitamin B 6 , vitamin B 12 , and alcohol and various forms of the MTHFR gene on risk of colon cancer. Individuals homozygous for the variant form of the MTHFR gene ( TT ) had a slightly lower risk of colon cancer than did individuals who were wild type [ CC , odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.6–1.1 for men; and OR = 0.9, 95% CI = 0.6–1.2 for women]. High levels of intake of folate, vitamin B 6 , and vitamin B 12 were associated with a 30–40% reduction in risk of colon cancer among those with the TT relative to those with low levels of intake who were CC genotype. Associations were stronger for proximal tumors, in which high levels of intake of these nutrients were associated with a halving of risk among those with the TT genotype. The inverse association with high levels of these nutrients in those with the TT genotype was stronger among those diagnosed at an older age. Although imprecise, the inverse association with the low-risk diet that was high in folate and methionine and without alcohol was observed for both the TT genotype (OR = 0.4 95% CI = 0.1–0.9) and the CC/CT genotype (OR = 0.6, 95% CI = 0.4–1.0), but this association was not seen with the high-risk diet for either the TT or CC/CT genotype. Although associations were generally weak, these findings suggest that those with differing MTHFR genotypes may have different susceptibilities to colon cancer, based on dietary consumption of folate, vitamin B 6 , and vitamin B 12 .