1. Genome scan study of prostate cancer in Arabs: identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians
- Author
-
Danny M. Rabah, Hala Kfoury, Shahzad Jafri, Issam Al-Bozom, Dhanya Kizhakayil, Idil I. Aigha, Hanif Khalak, Jillian Rowe, Karim Farhat, Lotfi Chouchane, Sami Alsaid, Shoba P Dsouza, Jingxuan Shan, and Khalid Al-Rumaihi
- Subjects
Male ,Tunisia ,Genotype ,Quantitative Trait Loci ,Population ,Saudi Arabia ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Prostate cancer ,Risk Factors ,medicine ,GWAS ,Arab population ,Humans ,Genetic Predisposition to Disease ,RNA, Messenger ,education ,Qatar ,Alleles ,Aged ,Oligonucleotide Array Sequence Analysis ,Aged, 80 and over ,Medicine(all) ,Genetics ,education.field_of_study ,Genome ,Biochemistry, Genetics and Molecular Biology(all) ,Research ,Chromosome Mapping ,Prostatic Neoplasms ,Reproducibility of Results ,General Medicine ,Prostate-Specific Antigen ,medicine.disease ,Arabs ,SNP genotyping ,Prostate-specific antigen ,Case-Control Studies ,Expression quantitative trait loci ,Genome-Wide Association Study ,SNP array - Abstract
Background 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. Methods Using 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. Results Three 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. Conclusion Our findings, identifying novel GWAS prostate cancer susceptibility loci, indicate that prostate cancer genetic risk factors could be ethnic specific.
- Published
- 2013
- Full Text
- View/download PDF