PurposeAlthough case–control studies have evaluated the role of variant inflammatory-related loci in prostate cancer, their impact is virtually unknown among men of African descent. To address this, we evaluated the impact of inflammatory cytokine single nucleotide polymorphisms (SNPs) on prostate cancer risk for men of African descent.MethodsForty-four SNPs in inflammatory cytokine-associated genes were evaluated among 814 African-American and Jamaican men (279 prostate cancer cases and 535 controls) using Illumina’s Golden gate genotyping system. Individual SNP effects were evaluated using logistic regression analysis.ResultsFour SNPs were modestly associated with prostate cancer after adjusting for age. In the total population, inheritance of the IL1R2 rs11886877 AA, IL8RB rs11574752 AA, TNF rs1800629 GA + AA, and TNF rs673 GA genotypes modestly increased prostate cancer risk by 1.45 to 11.7-fold relative to the referent genotype. Among U.S. men, age-adjusted dominant, recessive and additive genetic models for the IL1R2 rs11886877 locus were linked to an increase in prostate cancer susceptibility. However, these main effects did not persist after adjusting for multiple hypothesis testing.ConclusionOur preliminary data does not strongly support the hypothesis that inflammatory-related sequence variants influence prostate cancer risk among men of African descent. However, further evaluation is needed to assess whether other variant inflammatory-related genes may contribute to prostate cancer risk and disease progression in larger and ethnically diverse multi-center studies.

BACKGROUNDRecent advances demonstrate a relationship between chronic/recurrent inflammation and prostate cancer (PCA). Among inflammatory regulators, toll-like receptors (TLRs) play a critical role in innate immune responses. However, it remains unclear whether variant TLR genes influence PCA risk among men of African descent. Therefore, we evaluated the impact of 32 TLR-associated single nucleotide polymorphisms (SNPs) on PCA risk among African-Americans and Jamaicans.METHODSSNP profiles of 814 subjects were evaluated using Illumina’s Veracode genotyping platform. Single and combined effects of SNPs in relation to PCA risk were assessed using age-adjusted logistic regression and entropy-based multifactor dimensionality reduction (MDR) models.RESULTSSeven sequence variants detected in TLR6, TOLLIP, IRAK4, IRF3 were marginally related to PCA. However, none of these effects remained significant after adjusting for multiple hypothesis testing. Nevertheless, MDR modeling revealed a complex interaction between IRAK4 rs4251545 and TLR2 rs1898830 as a significant predictor of PCA risk among U.S. men (permutation testing p-value = 0.001).CONCLUSIONSMDR identified an interaction between IRAK4 and TLR2 as the best two factor model for predicting PCA risk among men of African descent. However, these findings require further assessment and validation.

BackgroundChemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs) are associated with various cancers, their impact on prostate cancer (PCA) among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses.MethodsSequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls) using Illumina’s Goldengate genotyping system.ResultsInheritance of CCL5 rs2107538 (AA, GA+AA) and rs3817655 (AA, AG, AG+AA) genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively.ConclusionsIn summary, CCL5 (rs2107538, rs3817655) and CCR5 (rs1799988) sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. 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.