Genome-wide association study of prostate cancer in Arab populations: Identification of three genomic regions with multiple consecutive prostate cancer susceptibility loci

Abstract

Background: Prostate cancer is the most common malignancy in many industrialized countries and the second cause of cancer-related death in Europe and the United States. The incidence of the disease has been increasing in Arab populations. Large 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. Genetic susceptibility to prostate cancer differs significantly across ethnicities. It would be of interest to identify the common alleles associated with prostate cancer risk in Arab population. Methods: With Affymetrix Genome-Wide Human SNP Array 6.0, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in a Tunisian cohort of 92 cases with prostate cancer and 131 age-matched controls. Then we extended the study to evaluate promising associations of 11 SNPs, identified by GWAS, in a cohort of individuals of Arab ancestry living in Qatar and Saudi Arabia (155 cases and 182 controls) using TaqMan® SNP Genotyping Assays. Results: We identified 3 consecutive regions significantly associated with prostate cancer risk on chromosome 9, 17 and 22, including 18 SNPs (P=8.52×10-5 to P=2.18×10-6) in the Tunisian population. Three previous reported common loci associated with prostate cancer at 17q21 containing STAT3 gene in the Caucasian population were confirmed. Two novel chromosomal regions associated with prostate cancer contain candidate susceptibility genes: SMARCA2, LOC646851and SUN2 were revealed. Conclusion: Our findings, identifying novel GWAS prostate cancer susceptibilty loci, indicate that prostate cancer genetic risk factors could be ethnic specific.