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  • Title: Genetic variants at 1q32.1, 10q11.2 and 19q13.41 are associated with prostate-specific antigen for prostate cancer screening in two Korean population-based cohort studies.
    Author: Kim S, Shin C, Jee SH.
    Journal: Gene; 2015 Feb 10; 556(2):199-205. PubMed ID: 25434496.
    Abstract:
    Prostate-specific antigen (PSA) levels are affected by non-cancerous conditions such as benign prostatic hyperplasia, inflammations, and inherited factors. To search for genetic variants associated with PSA levels, we conducted a genome-wide association study (GWAS) using a two-stage design. A total of 554 men from the Korean Cancer Prevention Study-II were used as a discovery stage and 1575 men collected by the Korean Genome Epidemiology Study were used as a replication stage. Analysis by Genome-wide Human single-nucleotide polymorphism (SNP) array 5.0 was performed by using DNAs derived from venous blood. We analyzed the association between genetic variants and PSA levels using multivariate linear regression models, including age as a covariate. We detected 12 genome-wide significant signals on chromosome 1q32.1, 10q11.2, and 19q13.41 between PSA levels and SNPs. The top SNP associated with log PSA levels was rs2153904 in SLC45A3 (p values, 5.24×10(-9) to 2.00×10(-6)). We also investigated GWAS using 754 subjects from KCPS-II cohort whether our genome-wide significant loci were associated with a risk of prostate cancer (PCa) (200 PCa cases and 554 controls). Three of the SNPs on 10q11.2, rs7077830, rs2611489, and rs4631830, were associated with a risk of PCa. However, two loci, 1q32.1 and 19q13, were not significantly associated with a PCa risk. We suggest that our results for some but not all PCa risk SNPs to be associated with PSA levels could be used as an evidence for the advance of individual PCa screening strategies, such as applying a personalized cutoff value for PSA.
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