Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism–related genes on the association of HCA intake with the risk of colorectal adenomas

Abstract

Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC. A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated by logistic regression analysis. CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend=0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p (Interaction)>0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance. HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.