Analysis of Prostate Cancer Susceptibility Variants in South African Men: Replicating Associations on Chromosomes 8q24 and 10q11.

Pedro Fernandez,Danielle Du Toit,Andre Van Der Merwe,Muneeb Salie

doi:10.1155/2015/465184

Pedro Fernandez, Danielle Du Toit + Show 2 more

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https://doi.org/10.1155/2015/465184

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Abstract

Genome-wide association studies (GWAS) have implicated single nucleotide polymorphisms (SNPs) on chromosomes 2p15, 6q25, 7p15.2, 7q21, 8q24, 10q11, 10q26, 11q13, 17q12, 17q24, 19q13, and Xp11, with prostate cancer (PCa) susceptibility and/or tumour aggressiveness, in populations of African, European, and Asian ancestry. The objective of this study was to confirm these associations in South African Mixed Ancestry and White men. We evaluated 17 prioritised GWAS SNPs in South African cases (331 Mixed Ancestry and 155 White) and controls (178 Mixed Ancestry and 145 White). The replicated SNP associations for the different South African ethnic groups were rs7008482 (8q24) (p = 2.45 × 10−5), rs6983267 (8q24) (p = 4.48 × 10−7), and rs10993994 (10q11) (p = 1.40 × 10−3) in Mixed Ancestry men and rs10993994 (p = 1.56 × 10−9) in White men. No significant associations were observed for the analyses stratified by disease aggressiveness in the individual and the combined population group analysis. The present study demonstrates that a number of known PCa susceptibility variants may contribute to disease susceptibility in South African men. Larger genetic investigations extended to other South African population groups are warranted to confirm the role of these and other SNPs in disease susceptibility.

Highlights

Prostate cancer (PCa) is the most frequently diagnosed cancer in men in developed countries, with higher incidence rates in the United States of America (USA) in individuals of African ancestry [1]
genome-wide association studies (GWAS) have generally been undertaken to a lesser extent in African descent populations, Prostate Cancer a recent meta-analysis of 82 PCa susceptibility variants identified primarily in GWAS in European and Asian descent populations generally demonstrated consistent replication of the direction of effects in men with African ancestry [30]
The median age at diagnoses of PCa cases and the median age of controls were significantly different among the groups; prostate specific antigen (PSA) levels were significantly different between the groups, with Mixed Ancestry controls and cases showing higher median levels (Table 1)

Summary

Introduction

Prostate cancer (PCa) is the most frequently diagnosed cancer in men in developed countries, with higher incidence rates in the United States of America (USA) in individuals of African ancestry [1]. Even though many of these associations exceeded or were close to genome-wide significance levels, it remains necessary to confirm these findings in multiple independent populations to rule out false positive results, thereby improving the likelihood that they represent true associations To this end, several studies have replicated GWAS associations in AA, EA, and Asian men [16,17,18,19,20,21,22,23,24,25,26,27,28,29]. GWAS have generally been undertaken to a lesser extent in African descent populations, Prostate Cancer a recent meta-analysis of 82 PCa susceptibility variants identified primarily in GWAS in European and Asian descent populations generally demonstrated consistent replication of the direction of effects in men with African ancestry [30]

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