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Abstract: To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10−4), rs7929962 at 11q13.3 (P = 2.7 × 10−4) and rs9364554 at 6q25.2 (P = 4.7 × 10−4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10−8) but 807 markers had P‐values <1 × 10−4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: There is evidence that prostate cancer (PCa) has a genetic predisposition, multiple genome-wide associations studies evaluating the impact of common and rare markers in the etiology of PCa and early-onset PCa. In our study we performed a genome-wide association scan for early-onset prostate cancer in a cohort of genotyped hospital patients form Romania. Used methodology: The study consisted of 2024 hospital patients genotyped, 990 unrelated PCa cases histopathologically confirmed and with abnormal PSA levels, and 1034 controls consisting of patients admitted for urological and surgical conditions, excluding cancer. Conclusions: We found genome-wide significant evidence for variants on chromosomes 2 ,12 and 22. We also evaluated the association results for the whole-genome obtaining compelling evidence regarding the importance of common genetic variants to early-onset PCa in Romania. [ABSTRACT FROM AUTHOR]

Objectives: There is evidence that prostate cancer (PCa) has a genetic predisposition, multiple genome-wide associations studies evaluating the impact of common and rare markers in the etiology of PCa and early-onset PCa. In our study we performed a genome-wide association scan for early-onset prostate cancer in a cohort of genotyped hospital patients form Romania. Used methodology: The study consisted of 2024 hospital patients genotyped, 990 unrelated PCa cases histopathologically confi rmed and with abnormal PSA levels, and 1034 controls consisting of patients admitted for urological and surgical conditions, excluding cancer. Conclusions: We found genome-wide signifi cant evidence for variants on chromosomes 2 ,12 and 22. We also evaluated the association results for the whole-genome obtaining compelling evidence regarding the importance of common genetic variants to early-onset PCa in Romania. [ABSTRACT FROM AUTHOR]