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.
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.
authors.affiliation: Department of Public Health, Graduate School, Yonsei University, Seoul, Republic of Korea; Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea.
authors.forename: Soriul
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Respiratory and Critical Care, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.affiliation: Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Republic of Korea. Electronic address: jsunha@yuhs.ac.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D002888:Chromosomes, Human, Pair 19; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D056910:Republic of Korea
chemical_list: D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; C551031:SLC45a3 protein, human; D017430:Prostate-Specific Antigen
keywords: Genetic risk score (GRS); Genome-wide association study; Prostate cancer; Prostate-specific antigen (PSA)