Interaction between vitamin E intake and a COMT gene variant on colorectal cancer risk among Korean adults: a case-control study

Abstract

OBJECTIVES: Previous human trials have not supported the anticarcinogenic effect of vitamin E despite biological plausibility and considerable epidemiological evidence. A possible explanation for this inconsistency is the interactive effect of the catechol-O-methyltransferase (COMT) gene and supplemental vitamin E on cancer. We examined whether a COMT gene variant modulates the effect of dietary vitamin E intake on colorectal cancer (CRC) risk. METHODS: In this case-control study of Korean adults (975 cases and 975 age- and sex-matched controls), dietary vitamin E density (mg/1,000 kcal) was measured using a semiquantitative food frequency questionnaire, COMT single nucleotide polymorphism (SNP) rs740603 (A > G) was genotyped, and CRC was verified histologically. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models with adjustments for potential confounders. RESULTS: Higher vitamin E density was associated with a lower risk of CRC (highest vs. lowest quartiles: OR, 0.72; 95% CI, 0.55 to 0.96; p-for-trend = 0.002). When stratified by COMT SNP rs740603 genotype, the inverse association between vitamin E density and CRC risk was confined to those with at least 1 A allele (≥ median vs. < median: OR, 0.63; 95% CI, 0.51 to 0.78). The interaction between rs740603 and vitamin E density was significant (p-for-interaction = 0.020). No direct association was observed between COMT SNP rs740603 and CRC risk (OR, 1.08; 95% CI, 0.83 to 1.41). CONCLUSIONS: Our findings support a role for a genetic polymorphism in COMT in modifying the association between dietary vitamin E intake and CRC.