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One-Carbon Metabolism Biomarkers and Risk of Colon and Rectal Cancers

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ² Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts; and ³ Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, Helsinki, Finland

Requests for reprints: Stephanie J. Weinstein, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Suite 320, 6120 Executive Boulevard, Bethesda, MD 20892. Phone: 301-594-7297; Fax: 301-496-6829. E-mail: weinstes{at}mail.nih.gov

Background: Folate intake has been associated with reduced colorectal cancer risk; however, few studies have prospectively examined circulating folate or other related one-carbon biomarkers.

Methods: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 50- to 69-year-old Finnish men to investigate associations between serum folate, vitamin B6, vitamin B12, riboflavin, and homocysteine and risk of colon and rectal cancers. Controls were alive and cancer-free at the time of case diagnosis and matched 1:1 on age and date of baseline fasting serum collection with cases (152 colon and 126 rectal cancers). Multivariate-adjusted odds ratios and 95% confidence intervals were calculated using conditional logistic regression.

Results: Serum vitamin B6 was inversely associated with colon cancer [odds ratio, 0.30 (95% confidence interval, 0.11-0.82) in the highest versus lowest quintile]. An increased risk of colon cancer was suggested for men in the middle quintile of serum folate, but without indication of a dose-response relationship. None of the other serum biomarkers were associated with colon or rectal cancer, and we observed no interactions with alcohol consumption or methionine or protein intake. A priori combinations of the five one-carbon serum biomarkers provided no clear evidence to support a collective influence on colorectal cancer risk.

Conclusions: Our results support the hypothesis that higher vitamin B6 status may play a role in inhibiting colon cancer carcinogenesis; however, folate and other one-carbon related biomarkers were not associated with colon or rectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3233–40)

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