P1.08 Identification of Three Genomic Regions with Multiple Consecutive Prostate Cancer Susceptibility Loci Through a Genome-Wide Association Study in ARAB Population

Abstract

ABSTRACT Introduction 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 Middle Eastern and North African (MENA) populations. Large databases focused on genetic susceptibility to prostate cancer have been accumulated from population studies of different ancestries, including Europeans and African-Americans. MENA populations, however, have been only rarely studied. Genetic susceptibility to prostate cancer differs significantly across ethnicities, e.g., the allele frequencies of the candidate prostate cancer susceptibility genes such as CYP3A4 and SRD5A2 differ substantially by ethnicity. It would be of interest to identify the common alleles associated with prostate cancer risk in MENA population. Material and Methods With Affymetrix SNP 6.0 chip, we conducted a genome-wide association study (GWAS) in which 534,781 single nucleotide polymorphisms (SNPs) were genotyped in a Tunisian cohort of 85 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. 11 out of these 18 SNPs are not associated with prostate cancer risk in the population living in Qatar and Saudi Arabia. Conclusions We confirmed previous reports of common loci associated with prostate cancer at 17q11 and 17q21 containing STAT5A and STAT3 in the Caucasian population. Moreover, we found that 2 new consecutive regions associated with prostate cancer contain candidate susceptibility genes: SMARCA2, GNAQ, SEPT9, MYO18B and SUN2. Additionally, our findings further proved that prostate cancer risky genetic factors are ethnic specific.