Sporadic microsatellite instability-high (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. Utilizing 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 (RR 0.79, 95% CI, 0.60-1.03 for microsatellite stable (MSS) /MSI-low colon cancers and RR 0.61, 95% CI, 0.37-1.02 for MSI-high colon cancers; Pheterogeneity = 0.53) or KRAS status (RR, 0.66, 95% CI, 0.49-0.87 for KRAS wildtype colon cancers and RR 1.05, 95% CI, 0.68-1.61 for KRAS mutated colon cancers; Pheterogeneity = 0.12), though our analyses had limited power to preclude an effect of folate on KRAS wildtype 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 appear to differ according to MSI or KRAS mutational status.
Keywords: methylgroup donors, one-carbon nutrients, folate, vitamin B6, p53, colon cancer