Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer.

Cancer Causes & Control : CCC
Aditi HazraShuji Ogino

Abstract

Dietary intake of one-carbon nutrients (methyl donors) and germline variants in the one-carbon metabolism genes may influence global DNA methylation level and methylation in promoter CpG islands. In this study, we evaluated the relationship between single nucleotide polymorphisms (SNPs) in the one-carbon metabolism pathway and DNA methylation status in colorectal cancer. Utilizing 182 colorectal cancers cases in two prospective cohort studies, we determined the CpG island methylator phenotype (CIMP) status on eight CIMP-specific promoters and measured LINE-1 methylation level that correlates well with genome-wide DNA methylation level. We genotyped 23 nonsynonymous SNPs in the one-carbon metabolism genes using buffy coat DNA. Most of the 23 SNPs in the one-carbon metabolism pathway were not significantly associated with CIMP-high status (> or = 6/8 methylated promoters). However, the MTHFR 429 Ala/Ala variant (rs1801131) and the TCN2 259 Arg/Arg variant (rs1801198) were associated with CIMP-high status (MTHFR 429 multivariate odds ratio (MV OR) = 7.56; 95% confidence interval (CI), 1.32-43.3; p trend = 0.10; TCN2 259 Arg/Arg variant MV OR = 3.82; 95% CI, 1.02-14.4; p trend = 0.06). The one-carbon metabolism genotypes were not s...Continue Reading

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