Abstract
BackgroundLarge databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. Arab populations, however, have been only rarely studied.MethodsUsing Affymetrix Genome-Wide Human SNP Array 6, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in 221 Tunisians (90 prostate cancer patients and 131 age-matched healthy controls). TaqMan® SNP Genotyping Assays on 11 prostate cancer associated SNPs were performed in a distinct cohort of 337 individuals from Arab ancestry living in Qatar and Saudi Arabia (155 prostate cancer patients and 182 age-matched controls). In-silico expression quantitative trait locus (eQTL) analysis along with mRNA quantification of nearby genes was performed to identify loci potentially cis-regulated by the identified SNPs.ResultsThree chromosomal regions, encompassing 14 SNPs, are significantly associated with prostate cancer risk in the Tunisian population (P = 1 × 10-4 to P = 1 × 10-5). In addition to SNPs located on chromosome 17q21, previously found associated with prostate cancer in Western populations, two novel chromosomal regions are revealed on chromosome 9p24 and 22q13. eQTL analysis and mRNA quantification indicate that the prostate cancer associated SNPs of chromosome 17 could enhance the expression of STAT5B gene.ConclusionOur findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.
Highlights
Prostate cancer (PCa) is the most common malignancy in western countries and the second cause of cancer-related death in Europe and the United States [1]
We further extended the study to evaluate potential associations of 11 single nucleotide polymorphisms (SNPs), identified by genome-wide association studies (GWAS), in a cohort from Arab ancestry living in Qatar and Saudi Arabia
Three consecutive regions were identified on chromosome 9, 17 and 22 encompassing 14 SNPs, which were found highly associated with prostate cancer (P = 1 × 10-4 to P = 1 × 10-5) (Table 2)
Summary
Prostate cancer (PCa) is the most common malignancy in western countries and the second cause of cancer-related death in Europe and the United States [1]. Little is known about the prostate cancer genetic susceptibility in populations of Arab ancestry. The genetic susceptibility to prostate cancer is variable among different populations [10]. Several SNPs located in 8q24 have been implied to a different population susceptibility to prostate cancer [11,12]. These variants, located in c-Myc gene, reduced the risk of prostate cancer in Caucasian but not in African Americans, protective mechanisms that might reduce c-Myc expression in Caucasians do not exist in African Americans. Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans.
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