PMID- 23359319 OWN - NLM STAT- MEDLINE DCOM- 20131113 LR - 20211021 IS - 1476-5586 (Electronic) IS - 1522-8002 (Print) IS - 1476-5586 (Linking) VI - 15 IP - 1 DP - 2013 Jan TI - Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA. PG - 95-101 AB - BACKGROUND: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. MATERIALS/METHODS: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P < 10(-5) were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. RESULTS: We identified two loci that were associated with %fPSA at a genome-wide significance level (P <5 x 10(-8)). The first associated SNP was rs3213764 (P = 6.45 x 10(-10)), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P = .015). The second locus was rs1354774 (P = 1.25 x 10(-12)), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. CONCLUSIONS: These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA. FAU - Jin, Guangfu AU - Jin G AD - Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. FAU - Zheng, Siqun Lilly AU - Zheng SL FAU - Lilja, Hans AU - Lilja H FAU - Kim, Seong-Tae AU - Kim ST FAU - Tao, Sha AU - Tao S FAU - Gao, Zhengrong AU - Gao Z FAU - Young, Tracey AU - Young T FAU - Wiklund, Fredrik AU - Wiklund F FAU - Feng, Junjie AU - Feng J FAU - Isaacs, William B AU - Isaacs WB FAU - Rittmaster, Roger S AU - Rittmaster RS FAU - Gronberg, Henrik AU - Gronberg H FAU - Condreay, Lynn D AU - Condreay LD FAU - Sun, Jielin AU - Sun J FAU - Xu, Jianfeng AU - Xu J LA - eng GR - R33 CA127768/CA/NCI NIH HHS/United States GR - P50-CA92629/CA/NCI NIH HHS/United States GR - P50 CA092629/CA/NCI NIH HHS/United States GR - R33 CA 127768-02/CA/NCI NIH HHS/United States GR - RC2 CA148463/CA/NCI NIH HHS/United States GR - UC2 CA148463/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (ATF7IP protein, human) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) RN - EC 3.4.21.35 (Tissue Kallikreins) RN - EC 3.4.21.77 (Prostate-Specific Antigen) SB - IM MH - Case-Control Studies MH - Genome-Wide Association Study/methods MH - Genotype MH - Humans MH - Male MH - Polymorphism, Single Nucleotide MH - Prostate-Specific Antigen/*blood MH - Prostatic Neoplasms/*blood/*genetics MH - Repressor Proteins MH - Sweden MH - Tissue Kallikreins/*genetics MH - Transcription Factors/*genetics PMC - PMC3556942 EDAT- 2013/01/30 06:00 MHDA- 2013/11/14 06:00 PMCR- 2013/01/01 CRDT- 2013/01/30 06:00 PHST- 2012/09/27 00:00 [received] PHST- 2012/11/15 00:00 [revised] PHST- 2012/11/15 00:00 [accepted] PHST- 2013/01/30 06:00 [entrez] PHST- 2013/01/30 06:00 [pubmed] PHST- 2013/11/14 06:00 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - 121620 [pii] AID - 10.1593/neo.121620 [doi] PST - ppublish SO - Neoplasia. 2013 Jan;15(1):95-101. doi: 10.1593/neo.121620.