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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.

Background: The use of the serum prostate-specific antigen (PSA) test for prostate cancer screening has resulted in a diagnostic dilemma: PSA is not prostate cancer specific and could be found in the normal prostate at equal or higher levels than is found in prostate cancer. Prostate cancer gene 3 (PCA3) encodes a prostate-specific mRNA with a median 66-fold up-regulation compared to adjacent benign tissue. In contrast, PSA gene expression is similar in cancerous and benign cells; PSA mRNA levels may therefore be used to normalize for the amount of prostate-specific ribonucleic acid (RNA) in molecular test samples. This report describes the characterization of a prototype quantitative PCA3-based test for whole urine. Methods: First-catch urine specimens were collected after digital rectal examination. The total RNA was isolated with Trizol, amplified, and quantified by use of a real-time PCR method. PSA mRNA concentrations were used to normalize PCA3 signals and confirm the yield of prostate-specific RNA. PCA3 score is calculated by one thousand times of PCA3/PSA mRNA ratio. ROC curve analysis is applied to determine the cutoff value of PCA3 score according to prostate biopsy results. Results: We have collected urine samples of 163 patients from uro-oncology clinic at Hamad Hospital. Due to the mixture of the blood cells and prostate cells in the urine, we failed to obtain RNA with proper quality for 29 samples. The specimen informative rate (fraction of specimens yielding proper RNA for analysis) was 82.2%. From ROC curve with the known diagnostic data, the cut off of PCA3 score is 1232 with a sensitivity of 70% and specificity of 68%. Conclusion: The established PCA3 assay could increase specificity to the current prostate cancer diagnosis. Comparing to the commercial kit, it provides equivalently useful information and it is much cheaper and faster. The challenge is to avoid the interference from the blood cells in the urine.