Genome scan study of prostate cancer in Arabs: Identification of three genomic regions with multiple prostate cancer susceptibility loci in Tunisians

Jingxuan Shan, Khalid Al-Rumaihi, Danny Rabah, Issam Al-Bozom, Dhanya Kizhakayil, Karim Farhat, Sami Al-Said, Hala Kfoury, Shoba P. Dsouza, Jillian Rowe, Hanif G. Khalak, Shahzad Jafri, Idil I. Aigha, Lotfi Chouchane

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number121
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
StatePublished - May 13 2013

Keywords

  • Arab population
  • GWAS
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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