title: Replication study of 34 common SNPs associated with prostate cancer in the Romanian population.
abstract: Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.
authors.affiliation: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Department, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
authors.forename: Viorel
authors.initials: V
authors.lastname: Jinga
authors.affiliation: National Institute of Public Health, Bucharest, Romania.
authors.forename: Irma Eva
authors.initials: IE
authors.lastname: Csiki
authors.affiliation: School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
authors.forename: Andrei
authors.initials: A
authors.lastname: Manolescu
authors.affiliation: School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
authors.forename: Paul
authors.initials: P
authors.lastname: Iordache
authors.affiliation: "St Mary" Clinical Hospital, General Surgery Department, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
authors.forename: Ioan Nicolae
authors.initials: IN
authors.lastname: Mates
authors.affiliation: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Department, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Radavoi
authors.affiliation: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Department, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rascu
authors.affiliation: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Department, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Badescu
authors.affiliation: National Institute of Public Health, Bucharest, Romania.
authors.forename: Paula
authors.initials: P
authors.lastname: Badea
authors.affiliation: National Institute of Public Health, Bucharest, Romania.
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D012383:Romania
chemical_list: D017430:Prostate-Specific Antigen
keywords: prostate cancer; replication; single nucleotide polymorphisms