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A Prospective Study of Dietary Folate and Vitamin B and Colon Cancer According to Microsatellite Instability and KRAS Mutational Status

¹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, ² Department of Epidemiology, Harvard School of Public Health, ³ Department of Medical Oncology, Dana-Farber Cancer Institute, and ⁴ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and ⁵ Ludwig Boltzmann-Institute for Applied Cancer Research, KFJ-Spital, Vienna, Austria and Applied Cancer Research-Institute for Translational Research Vienna, Vienna, Austria

Requests for reprints: Eva S. Schernhammer, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-4648; Fax: 617-525-2008; E-mail: eva.schernhammer{at}channing.harvard.edu

Sporadic microsatellite instability (MSI)-high colon cancers are positively associated with MLH1 promoter methylation and inversely with KRAS mutation. One-carbon metabolism is critical for methylation reactions and nucleotide biosynthesis, but the influence of dietary one-carbon nutrients such as folate and B vitamins on molecular changes in colon cancer is not known. Using the database of two independent prospective cohort studies (88,691 women and 47,371 men), we examined the relation between dietary intake of one-carbon nutrients and the incidence of microsatellite instability and KRAS mutation in 669 incident colon cancers. The overall inverse association between folate and colon cancer did not differ significantly according to MSI status [relative ratio (RR), 0.79; 95% confidence interval (95% CI), 0.60-1.03 for microsatellite stable/MSI-low colon cancers; and RR, 0.61, 95% CI, 0.37-1.02 for MSI-high colon cancers; P_{heterogeneity} = 0.53] or KRAS status (RR, 0.66; 95% CI, 0.49-0.87 for KRAS wild-type colon cancers; and RR, 1.05; 95% CI, 0.68-1.61 for KRAS mutated colon cancers; P_{heterogeneity} = 0.12), although our analyses had limited power to preclude an effect of folate on KRAS wild-type colon cancers. Similarly, high vitamin B₆ or B₁₂ intake was inversely associated with colon cancers, regardless of MSI or KRAS status. No significant effect of methionine intake or alcohol consumption was observed for colon cancers with MSI high or KRAS mutation. In conclusion, the influence of dietary one-carbon nutrient intake on colon cancer risk does not seem to differ according to MSI or KRAS mutational status. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2895–8)