Abstract 4605: Variation in genes involved in the immune response and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial

Abstract

Abstract Background: We previously found that inflammation in benign prostate tissue is associated with increased odds of prostate cancer especially higher-grade disease. To understand this link, we evaluated the association between single nucleotide polymorphisms (SNPs) in immune response genes and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). Men were screened yearly and if not diagnosed with prostate cancer during the trial, underwent an end-of-study biopsy. Thus, in a subanalysis, we were able to study associations in men with low PSA; i.e., men in whom bias due to any link between inflammation and elevated PSA, an indication for biopsy, is reduced. Methods: We genotyped 16 candidate SNPs in IL1b, IL2, IL4, IL6, IL8, IL10, IL12(p40), IFNG, MSR1, RNASEL, TLR4, and TNFA and 7 tagSNPs in IL10 in 881 prostate cancer cases and 848 controls negative for cancer on an end-of-study biopsy. Cases and controls were non-Hispanic white and frequency matched on age and family history. We classified cases as lower (Gleason sum <7; N = 674) and higher (7-10; N = 172) grade. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age and family history. Results: The minor allele (C) of rs3212227 in IL12(p40) was associated with an increased risk of total (log additive: OR = 1.30, 95% CI 1.10-1.53; P-trend = 0.0017) and lower-grade (OR = 1.36, 95% CI 1.15-1.62; P-trend = 0.0004) prostate cancer. The minor allele (A) of rs4073 in IL8 was possibly associated with a decreased risk of higher-grade (OR = 0.81, 95% CI 0.64-1.02; P-trend = 0.07), but not total disease. None of the other candidates was associated with risk. The minor alleles of IL10 tagSNPs rs1800890 (A; OR = 0.87, 95% CI: 0.75-0.99; P-trend = 0.04) and rs3021094 (C; OR = 1.31, 95% CI 1.03-1.66, P-trend = 0.03) were associated with prostate cancer risk; the latter also with lower- (P-trend = 0.04) and possibly higher- (P-trend = 0.06) grade disease. These patterns were generally similar among men with prostate specific antigen (PSA)<2 ng/mL at biopsy. Conclusion: Our study suggests that variation in some immune response genes possibly may be associated with prostate cancer risk. These associations were not fully explained by PSA-associated detection bias as they remained in men with low PSA. Our findings provide some support to inflammation's role in the etiology of prostate cancer. Funding: P01 CA108964, U10 CA37429, UM1 CA182883, T32 CA009314. *A SWOG-Coordinated Study S9217 Citation Format: Danyelle A. Winchester, Cathee Till, Phyllis J. Goodman, Catherine M. Tangen, Regina M. Santella, Teresa L. Johnson-Pais, Robin J. Leach, Jianfeng Xu, S. Lilly Zheng, Ian M. Thompson, M. Scott Lucia, Scott M. Lippmann, Howard L. Parnes, Paul J. Dluzniewski, William B. Isaacs, Angelo M. De Marzo, Charles G. Drake, Elizabeth A. Platz. Variation in genes involved in the immune response and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4605. doi:10.1158/1538-7445.AM2015-4605