Chemokine Ligand 5 (CCL5) and chemokine receptor (CCR5) genetic variants and prostate cancer risk among men of African Descent: a case-control study
1 Department of Pharmacology & Toxicology, University of Louisville Clinical Translational Research Building, 505 South Hancock Street Room 306, Louisville, KY, 40202, USA
2 Biomedical/Biotechnology Research Institute (BBRI), North Carolina Central University, 531 Nelson Street, Durham, NC, 27707, USA
3 Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA
4 Department of Community Health and Psychiatry, University of West Indies, Ring Road, Mona, Jamaica
5 Department of Bioinformatics & Biostatistics, University of Louisville, School of Public Health & Information Sciences, 485 East Gray Street, Louisville, KY, 40202, USA
6 School of Medicine, University of Louisville, 323 East Chestnut Street, Louisville, KY, 40292, USA
Hereditary Cancer in Clinical Practice 2012, 10:16 doi:10.1186/1897-4287-10-16Published: 20 November 2012
Chemokine 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.
Sequence 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.
Inheritance 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.
In 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.