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MTHFR Genotype and Colorectal Adenoma Recurrence: Data from a Double-blind Placebo-controlled Clinical Trial

¹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Departments of ² Community and Family Medicine, and ³ Medicine, Dartmouth Medical School, Hanover, New Hampshire; ⁴ SAIC-Frederick, Inc. NCI-Frederick, Frederick, Maryland; ⁵ Department of Medicine, University of Toronto, Toronto, Ontario, Canada; ⁶ Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; ⁷ Laboratory of Molecular Technology, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland; ⁸ Section of Pharmacology, Institute of Medicine, University of Bergan and Haukeland University Hospital, Bergan, Norway; and ⁹ Department of Mathematics and Statistics, College of Engineering and Mathematical Sciences, University of Vermont, Burlington Vermont

Requests for reprints: A. Joan Levine, USC/Keck School of Medicine, University of Southern California, Topping Tower, 1441 Eastlake Avenue, Los Angeles, CA 90033. Phone: 323-865-0402; Fax: 323-865-0140. E-mail: ajoanlev{at}usc.edu

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. We assessed the association between two common MTHFR variants, 677C>T and 1298A>C, and adenoma recurrence in the context of a randomized double- blind clinical trial of aspirin use and folate supplementation. We used generalized linear regression to estimate risk ratios and 95% confidence intervals (95% CI) for recurrence, adjusting for age, sex, clinical center, follow-up time, and treatment status. Neither MTHFR polymorphism was associated with overall or advanced adenoma recurrence. Compared with those with two wild-type alleles, the relative risk for advanced adenoma was 0.75 (95% CI, 0.36-1.55) for the MTHFR 677 TT genotype and 1.16 (95% CI, 0.58-2.33) for the MTHFR 1298 CC genotype. The effect of folate supplementation on recurrence risk did not differ by genotype. Our findings indicate that the MTHFR genotype does not change adenoma risk in a manner similar to its effect on colorectal cancer, and does not modify the effect of folate supplementation on metachronous adenoma risk. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2409–15)