AMACRPolymorphisms,Dietary Intake of RedMeat.pdf

The Prostate 71:498 ^506 (2011) AMACRPolymorphisms,Dietary Intake of RedMeat andDairyand ProstateCancerRisk Jonathan L. Wright,1,2* Marian L. Neuhouser,2 Daniel W. Lin,1,2 Erika M. Kwon,3 Ziding Feng,2 Elaine A. Ostrander,3 and Janet L. Stanford2,4 1DepartmentofUrology,UniversityofWashington SchoolofMedicine, Seattle,Washington 2Divisionof PublicHealth Sciences, FredHutchinsonCancer ResearchCenter, Seattle,Washington 3CancerGenetics Branch,NationalHumanGenomeResearch Institute,Bethesda,Maryland 4Departmentof Epidemiology, Schoolof PublicHealth,UniversityofWashington, Seattle,Washington BACKGROUND. Alpha-methylacyl CoA racemase (AMACR) is an enzyme involved in fatty acids metabolism. One of AMACRs primary substrates, phytanic acid, is principally obtained from dietary red meat/dairy, which are associated with prostate cancer (PCa) risk. AMACR is also a tumor tissue biomarker over-expressed in PCa. In this study, we explored the potential relationship between AMACR polymorphisms, red meat/dairy intake, and PCa risk. METHODS. Caucasian participants from two population-based PCa case–control studies were included. AMACR single nucleotide polymorphisms (SNPs) were selected to capture variation across the gene and regulatory regions. Red meat and dairy intake was determined from food frequency questionnaires. The odds ratio (OR) of PCa (overall and by disease aggressiveness) was estimated by logistic and polytomous regression. Potential interactions between genotypes and dietary exposures were evaluated. RESULTS. Data from 1,309 cases and 1,267 controls were analyzed. Carriers of the variant T allele (rs2287939) had an OR of 0.81 (95% CI 0.68–0.97) for less aggressive PCa, but no alteration in risk for more aggressive PCa. Red meat consumption was positively associated with PCa risk, and the association was stronger for more aggressive disease (lowest vs. highest tertile OR? 1.55, 95% CI 1.10–2.20). No effect modification of AMACR polymorphisms by either dietary red meat