Stella Koutros

NCI, DCEG, OEEB

PLCO (Learn more about this study)

2007-0029

Jun 12, 2007

Xenobiotic Metabolizing Gene Variants, Dietary Meat Mutagen Intake and Risk of Prostate Cancer

Meats cooked at high temperatures, such as pan-frying or grilling, are a source of carcinogenic heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). The chemical activation and metabolic detoxification of these meat mutagens are dependent on particular xenobiotic metabolizing enzymes. Single nucleotide polymorphisms (SNPs) in genes that code for phase I and II enzymes directly involved in the metabolism of these compounds may cause decreased or increased enzyme expression or complete absence of the enzyme, resulting in differential mutagen metabolism and thus differential risks for prostate cancer. We propose to evaluate the interaction between meat mutagen intake and gene variants involved in mutagen metabolism and risk of prostate cancer. Unconditional logistic regression will be used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between meat mutagen intake, polymorphisms, and prostate cancer, controlling for covariates. Gene-mutagen interactions will be examined using a multiplicative model. Interactions will be assessed by including the cross-product terms for the gene (SNPs or haplotypes) and mutagen intake as well as the main effect terms in a logistic regression model. Since previous findings from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial have implicated the HCA PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) we hope to evaluate whether certain gene variants modify this association in particular.