Heterocyclic aromatic amine [HCA] intake and prostate cancer risk: effect modification by genetic variants.Nutr Cancer 2012; 64(5):704-13NC
The association between heterocyclic aromatic amine (HCA) intake and prostate cancer (PCa) risk may be modified by genetic variation in enzymes involved in HCA metabolism. We examined this question in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition Heidelberg cohort. The study included 204 PCa cases and 360 matched controls. At baseline, participants provided dietary and lifestyle data and blood samples that were used for genotyping. Dietary HCA intake-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo [4,5-f]quinoxaline (DiMeIQx-was estimated using information on meat consumption, cooking methods, and browning degree. Risk estimates for gene × HCA interactions were calculated by unconditional logistic regression. We found inverse associations between PhIP, MeIQx, or DiMeIQx intake and PCa risk when having <2 deletions of the GSTT1 and GSTM1 genes (P(interaction): 0.03, 0.01, and 0.03, respectively), which is supported by analysis of darkly browned meat consumption data. Statistically significant effect modification of both HCA (DiMeIQx) and darkly browned meat intake and PCa risk was observed for allelic variants of MnSOD (rs4880) (P(interaction): 0.02). Despite limitations due to study size, we conclude that the association between HCA intake and PCa risk could be modified by polymorphisms of GSTT1, GSTM1, and MnSOD.