Abstract 2847: TagSNPs in the podocalyxin (PODXL) gene are associated with prostate cancer risk

Abstract

Abstract Previous gene mapping efforts, including a recent admixture mapping study, concluded that there is likely at least one prostate cancer susceptibility locus on 7q32. Podocalyxin (PODXL) is the strongest candidate gene in this region, particularly for risk of aggressive disease (Casey et al. Human Molecular Genetics, 5: 735-741, 2006). Therefore, we examined 34 tagSNPs in the PODXL gene in relation to prostate cancer risk and aggressiveness in a sample of unrelated cases (n=626) and controls (n=239) from metropolitan Detroit, MI. Men were recruited from Henry Ford Health System; cases were diagnosed with prostate cancer between 2001 and 2004, and controls were frequency matched to cases on 5 year age groups and race. Logistic regression models were adjusted for family history of prostate cancer, race, age, and ancestry where appropriate. Carrying at least one copy of the variant A allele in SNP rs3212299 was associated with a decrease in prostate cancer risk (OR=0.60, 95% CI: 0.41, 0.90). Having at least on copy of the C allele in SNP rs11773254 was associated with a 70% increased risk of prostate cancer (OR = 1.70, 95% CI: 1.13, 2.58). The G allele of rs1733874 was marginally protective in the entire sample (OR=0.74, 95% CI: 0.49, 1.02). These risk estimates did not appreciably vary after stratifying by race [African American (AA), European American (EA)], age (< age 62, > age 62), or prostate cancer aggressiveness (Gleason sum 3+4 or lower, Gleason sum 4+3 or higher). In addition, a protective effect of the C allele in SNP rs3800684 was observed in AA men (OR=0.56, 95% CI: 0.35, 0.90) but not in EA men (OR=1.38, 95% CI: 0.92, 2.09), and there was a statistically significant interaction between race and genotype at this marker (p=0.005). After stratifying by median age, the A allele of SNP rs10224884 was marginally associated with increased prostate cancer risk in the older age group (OR=1.44, 95% CI : 0.92, 2.27), but not the younger age group (OR=0.69, 95% CI: 0.42, 1.13), and the interaction between age group and genotype was statistically significant (0.03). Overall, we conclude that SNPs in the PODXL gene are associated with prostate cancer risk, but not prostate cancer aggressiveness, and that some of these variants may have race- and age-specific effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2847.