A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma.
We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.
Chen
J
J
Department of Epidemiology, Harvard School of Public Health, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA 02115, USA. jia.chen@mountsinai.org
Giovannucci
E
E
Hankinson
S E
SE
Ma
J
J
Willett
W C
WC
Spiegelman
D
D
Kelsey
K T
KT
Hunter
D J
DJ
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000236:Adenoma / Q000201:enzymology* / Q000235:genetics; D000328:Adult; D015179:Colorectal Neoplasms / Q000196:embryology* / Q000235:genetics; D000431:Ethanol / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors
D000431:Ethanol; D005492:Folic Acid; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase