Abstract 924: Possible joint effects between single nucleotide polymorphisms in inflammation genes and serum androgen levels on risk of prostate cancer

Abstract

Abstract Both inflammation and androgens are likely to be involved in the etiology of prostate cancer. There is evidence for cross-talk between androgen and inflammation pathways, yet little is known about the joint contribution of inflammation and androgens to prostate cancer risk. Thus, we evaluated the joint effects of 9,932 tag single nucleotide polymorphisms (SNPs) in 774 inflammation-related genes and four serum androgen measures (total testosterone [T], bioavailable T, 3α-androstanediol glucuronide [3α diol G], and androstenedione) on risk of prostate cancer in 516 incident cancer cases and 560 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. SNPs included in this study were genotyped as part of the National Cancer Institute Cancer Genetic Markers of Susceptibility genome-wide association study. Likelihood ratio tests (LRT) were used to compare logistic models of prostate cancer regressed on age, center, the androgen (in quartiles), the SNP (additive genetic coding) and the SNP x hormone interaction term to logistic models of prostate cancer regressed on age, center, and the androgen. False discovery rate (FDR) control was used to adjust for multiple testing. Statistically significant LRT P-values were noted for T and three intronic SNPs in linkage disequilibrium (r2>0.7) within the HIPK2 gene on 7q34 (rs10256326, rs7788362, and rs12539357; FDR-adjusted P=0.04 for all SNPs). For each SNP, the minor allele was associated with a reduced prostate cancer risk in men with serum T levels in the lower three quartiles, but was associated with an increased risk among men in the highest quartile of serum T. LRT P-values of borderline statistical significance were also seen for joint effects of these three SNPs and bioavailable T on risk of prostate cancer (FDR-adjusted P=0.07 for all SNPs). There were no significant joint effects for any of the SNPs with 3αdiol G or androstenedione after adjustment for multiple tests. Our preliminary results suggest that T levels could interact with HIPK2 gene variants to influence prostate cancer risk. HIPK2 is an attractive candidate gene for further evaluation because it codes for a serine/threonine kinase involved in transcriptional regulation, particularly involved in p53-dependent and independent regulation of cell cycle control and apoptosis. Future studies are needed to confirm our preliminary findings and to further understand the possible interaction between T and genetic variants in HIPK2, which could contribute to prostate cancer risk. 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 924.