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Background  One-carbon metabolism appears to play an important role in DNA methylation reaction. Evidence suggests that a low intake of B vitamins or high alcohol consumption increases colorectal cancer risk. How one-carbon nutrients affect the CpG island methylator phenotype (CIMP) or  BRAF  mutation status in colon cancer remains uncertain.    Methods  Utilizing incident colon cancers in a large prospective cohort of women (the Nurses' Health Study), we determined  BRAF  status (N = 386) and CIMP status (N = 375) by 8 CIMP-specific markers [ CACNA1G ,  CDKN2A  (p16),  CRABP1 ,  IGF2 ,  MLH1 ,  NEUROG1 ,  RUNX3 , and  SOCS1 ], and 8 other CpG islands ( CHFR ,  HIC1 ,  IGFBP3 ,  MGMT , MINT-1, MINT-31, p14, and  WRN ). We examined the relationship between intake of one-carbon nutrients and alcohol and colon cancer risk, by  BRAF  mutation or CIMP status.    Results  Higher folate intake was associated with a trend towards low risk of CIMP-low/0 tumors [total folate intake ≥400 µg/day vs. <200 µg/day; the multivariate relative risk = 0.73; 95% CI = 0.53–1.02], whereas total folate intake had no influence on CIMP-high tumor risks (P heterogeneity  = 0.73). Neither vitamin B 6 , methionine or alcohol intake appeared to differentially influence risks for CIMP-high and CIMP-low/0 tumors. Using the 16-marker CIMP panel did not substantially alter our results. B vitamins, methionine or alcohol intake did not affect colon cancer risk differentially by  BRAF  status.    Conclusions  This molecular pathological epidemiology study suggests that low level intake of folate may be associated with an increased risk of CIMP-low/0 colon tumors, but not that of CIMP-high tumors. However, the difference between CIMP-high and CIMP-low/0 cancer risks was not statistically significant, and additional studies are necessary to confirm these observations.

B Vitamins, Methionine and Alcohol Intake and Risk of Colon Cancer in Relation to BRAF Mutation and CpG Island Methylator Phenotype (CIMP)