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

The Chinese University of Hong Kong, Hong Kong
PLoS ONE (Impact Factor: 3.23). 06/2011; 6(6):e21102. DOI: 10.1371/journal.pone.0021102
Source: PubMed


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.
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.
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.
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.

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    • "Lower blood folate levels are associated with global DNA hypomethylation in both tumour tissue and blood [53] [55], and lower folate intake with increased risk of LINE-1 hypomethylation [54]. However, there is conflicting evidence from studies nested within prospective cohorts as to whether high [56] or low [57] folate levels are associated with CIMP-positive tumours. "
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    • "In the female cohort members, no dietary consumptions were identified which were associated with BRAF mutations. An additional assessment of 86 BRAF mutated and 300 BRAF wildtype colonic cancers failed to identify an association between alcohol, folate, vitamins B6 and B12 or methionine consumption and BRAF mutation status (Schernhammer et al., 2011). Another study population, of which 1108 cases of CRC were assessed for the presence of BRAF mutations, identified no associations between the 114 cancers harbouring this genetic lesion and intake of either vitamins B6, B12, folate, methionine or fibre consumptions, when compared with non-cancerous controls (Slattery et al., 2007). "

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