Abstract 2618: Chemokine-associated loci and prostate cancer among men of African descent

Abstract

Abstract Recent research efforts have focused on the identification of genetic determinants of prostate cancer (PCA). Emphasis has been placed on genes that encode chemokines and their receptors, since they play an essential role in tumorigenesis. This study seeks to evaluate the individual and combined effects of 42 single nucleotide polymorphisms (SNPs) in chemokine associated genes in relation to PCA outcomes among 814 African-American, African and Jamaican men. We hypothesized individuals inheriting chemokine-associated loci (linked to increased inflammation, immune response, metastasis and cell survival) will have an increased risk of developing PCA and/or aggressive disease relative to individuals expressing the referent genotypes. Forty-two SNPs detected in chemokine-associated genes were evaluated in germ-line DNA samples collected from 279 PCA cases and 535 controls using Illumina's Veracode genotyping system. Study participants were recruited from cancer screening programs, hospitals, or cancer centers located in the D.C., South Carolina, and Kingston, Jamaica. Genotyping was performed by Expression Analysis, Inc. Main effects were evaluated using logistic regression analysis (LR). Among US men, inheritance of one or more CCL5 rs2280789G (OR= 0.60; 95% CI=0.40, 0.90), CCL5 rs3817655A (OR = 0.56; 95%CI = 0.39, 0.81), CCL5 rs2107538G (OR = 0.66; 95%CI = 0.46, 0.96), and CCL25 rs2032887G (OR= 0.66; 95% CI=0.46, 0.96) alleles were significantly associated with a 32-56% reduction in the risk of developing PCA with P-values ranging from 0.027-0.0001. For Jamaican men, there was a two-fold increase in PCA susceptibility associated with CCR5 rs1799988 under the recessive genetic model (OR=1.96; 95% CI=1.04, 3.70) as well as the CCR7 rs3136685 TC+CC (OR=2.3; 95% CI=1.05, 5.07) and CCR5 rs1799987 AA genotypes (OR=2.18; 95% CI=1.04, 4.58). However, the CCR9 rs1488371 CA+AA genotype (OR=0.6; 95% CI=0.23, 0.94) was related to a 40% reduction in PCA among Jamaicans. With the exception of CCR5 rs1799987 and CCL25 rs2032887, the aforementioned relationships persisted after adjusting for potential confounders (i.e., age, family history of prostate cancer). In summary, polymorphisms in chemokine-associated genes modify PCA susceptibility among men of African descent in the current study. In larger ongoing studies, we will evaluate main and joint modifying effects in relation to high tumor grade, biochemical/disease recurrence, and disease-specific/overall mortality. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent. [[Unsupported Character -  ]] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2618. doi:1538-7445.AM2012-2618