Xenobiotic metabolizing genes, meat-related exposures, and risk of advanced colorectal adenoma

Abstract

Objectives: Carcinogenic action of meat-related exposures, such as heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and N-nitroso compounds (NOCs), might explain positive associations between red and processed meat and colorectal neoplasia. Single nucleotide polymorphisms in xenobiotic metabolizing enzyme (XME) genes could alter activation/detoxfication of these compounds.

Methods: We evaluated interactions between several XME genes (CYP1A1, CYP1B1, CYP2A6, CYP2C9, CYP2E1, CYP3A4, EPHX1, GSTM1, GSTM2, GSTT1, NAT1, NAT2, NQO1, SULT1A1, and SULT1A2) and meat-related exposures using a pathway-based approach in 720 advanced colorectal adenoma cases of the distal colon or rectum and 746 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Using meat-related databases, we estimated intake of the HCAs, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), the PAH, benzo[a]pyrene (B[a]P), and nitrate/nitrite, as NOC precursors.

Results: There were possible interactions between PhIP and CYP1B1 (P_interaction=0.019) and NQO1 (P_interaction=0.007), B[a]P and CYP1B1 (P_interaction=0.005) and CYP3A4 (P_interaction=0.021), and nitrate/nitrite and CYP1A1 (P_interaction=0.022) in relation to colorectal adenoma. However, none of these interactions were statistically significant using a false discovery rate threshold of 0.20.

Conclusions: Common variants in XME genes may modify the association of HCAs, PAHs, and nitrate/nitrite with advanced colorectal adenoma, but investigation in other populations is required, especially within consortia.