Abstract 812: Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to finasteride in the Prostate Cancer Prevention Trial

Abstract

Abstract Background: We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer in the Prostate Cancer Prevention Trial* (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk in men randomized to finasteride, which is known to increase intraprostatic inflammation. Methods: 16 candidate SNPs in IL1, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and 7 tagSNPs in IL10 were genotyped in 625 prostate cancer cases, and 532 controls negative for cancer on an end-of-study biopsy nested in the PCPT finasteride arm. Cases and controls were non-Hispanic white men. We used logistic regression to estimate log-additive odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history (matching factors). Results: Minor alleles of rs2243250 (T) in IL4 (OR = 1.46, 95% CI 1.03-2.08, P-trend = 0.03), rs1800896 (G) in IL10 (OR = 0.77, 95% CI 0.61-0.96, P-trend = 0.02), rs2430561 (A) in IFNG (OR = 1.33, 95% CI 1.02-1.74; P-trend = 0.04), rs3747531 (C) in MSR1 (OR = 0.55, 95% CI 0.32-0.95; P-trend = 0.03), and possibly rs4073 (A) in IL8 (OR = 0.81, 95% CI 0.64-1.01, P-trend = 0.06) were associated with higher- (Gleason 7-10; N = 222), but not lower- (Gleason 2-6; N = 380) grade prostate cancer. In men with low PSA (<2 ng/mL), these associations were attenuated and/or no longer significant, whereas inverse associations with higher-grade disease were apparent for minor alleles of rs1800795 (C: OR = 0.70, 95% CI 0.51-0.94, P-trend = 0.02) and rs1800797 (A: OR = 0.72, 95% CI 0.53-0.98, P-trend = 0.04) in IL6. While some IL10 tagSNPs were associated with lower- and higher-grade prostate cancer, distributions of IL10 haplotypes did not differ from controls, except possibly among those with low PSA (P = 0.07). Conclusion: In the PCPT finasteride arm, variation in genes involved in the immune response, including possibly IL8 and IL10 as in the placebo arm, may be associated with prostate cancer, especially higher-grade disease, but we cannot rule out PSA-associated detection bias or chance due to multiple testing.Funding: P01 CA108964, U10 CA37429, UM1 CA182883, T32 CA009314. *A SWOG-Coordinated Study S9217 Citation Format: Danyelle A. Winchester, Cathee Till, Jianfeng Xu, Ian M. Thompson, Scott M. Lippmann, Howard L. Parnes, Angelo M. De Marzo, Charles G. Drake, Elizabeth A. Platz, The PCPT P01 Project 4 Research Team. Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to finasteride in the Prostate Cancer Prevention Trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 812.