Chemokine Ligand 5 (CCL5) and chemokine receptor (CCR5) genetic variants and prostate cancer risk among men of African Descent:a case-control study

Abstract

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.

Inflammation polymorphisms and prostate cancer risk in Jamaican men: Role of obesity/body size

“…While many studies have focused on the association of PC risk with obesity, sequence variants, and other risk factors, very few reports have shed light on the underlying interactions among the aforementioned risk factors in relation to PC susceptibility and disease progression. We have previously published on SNPs of inflammatory related genes and PC risk [Jones, et al 2013; Kidd, et al 2012]. Also, we have previously reported positive correlations with PC risk and Waist to Hip Ratio (WHR) in this current study population [Jackson, et al 2010].…”

“…These 515 individuals comprise of 211 Jamaican black men and 304 US black men [Jones, et al 2013; Kidd, et al 2012]. Details of the Jamaican study subset (case and control ascertainment, inclusion criteria) have been previously published elsewhere [Jackson, et al 2012].…”

“…Criteria of SNP selection, quality control, data management of genotype data, testing for Hardy Weinberg equilibrium are documented in our previously published studies [Jones, et al 2013; Kidd, et al 2012]. Genotyped data used in this study were combined from the above mentioned published studies for a total of 87 (43 chemokine related and 44 cytokine related) SNPs.…”

“…However, in obesity, owing to the changes in cytokine profile, the resident macrophages in the white adipose tissue release pro-inflammatory cytokines [Balkwill and Mantovani 2001]. This imbalance in inflammatory and immune surveillance pathways in chronic inflammation possibly leads to development/progression of cancer [Kidd, et al 2012]. …”

IRAK4 and TLR3 Sequence Variants may Alter Breast Cancer Risk among African-American Women

“…Dysregulation of and genetic alterations in inflammation and immune response pathways have been linked with cancer susceptibility (6–9, 28). Although African-American women suffer disproportionately from more deadly forms of BrCa, only one study has explored the involvement of a single TLR-associated SNP ( TLR1/TLR6/TLR10 rs7696175) in relation to BrCa among this high risk sub-group (19).…”