@article{50f014541f3d4611ab3e3d69ef0ac85d,
title = "Genome-wide association study identifies genetic determinants of urine PCA3 levels in men",
abstract = "Prostate cancer gene 3 (PCA3) is a non-coding gene specifically overexpressed in prostate cancer (PCa) that has great potential as a clinical biomarker for predicting prostate biopsy outcome. However, genetic determinants of PCA3 expression level remain unknown. To investigate the association between genetic variants and PCA3 mRNA level, a genome-wide association study was conducted in 1371 men of European descent in the REduction by DUtasteride of prostate Cancer Events trial. First-voided urine specimens containing prostate cells were obtained after digital rectal examination. The PROGENSA PCA3 assay was used to determine PCA3 score in the urinary samples. A linear regression model was used to detect the associations between (single nucleotide polymorphisms) SNPs and PCA3 score under an additive genetic model, adjusting for age and population stratification. Two SNPs, rs10993994 in β-microseminoprotein at 10q11.23 and rs10424878 in kallikrein-related peptidase 2 at 19q13.33,were associated with PCA3 score at genome-wide significance level (P = 1.22 × 10-9 and 1.06 × 10-8, respectively). Men carrying the rs10993994 {"}T{"} allele or rs10424878 {"}A{"} allele had higher PCA3 score compared with men carrying rs10993994 {"}C{"} allele or rs10424878 {"}G{"} allele (β = 1.25 and 1.24, respectively). This is the first comprehensive search for genetic determinants of PCA3 score. The novel loci identified may provide insight into the molecular mechanisms of PCA3 expression as a potential marker of PCa.",
author = "Zhuo Chen and Jielin Sun and Kim, {Seong Tae} and Jack Groskopf and Junjie Feng and Isaacs, {William B.} and Rittmaster, {Roger S.} and Condreay, {Lynn D.} and Zheng, {Siqun Lilly} and Jianfeng Xu",
note = "Funding Information: Abbreviations: GWAS, genome-wide association study; REDUCE, REduction by DUtasteride of prostate Cancer Events; PCa, prostate cancer; PSA, prostate-specific antigen; PCA3, prostate cancer gene 3; MSMB, β-microseminoprotein; KLK2, kallikrein-related peptidase 2; KLK3, kallikrein-related peptidase 3; IPSS, International Prostate Symptom Score Address all correspondence to: Dr Jianfeng Xu or Dr Siqun Lilly Zheng, Center for Cancer Genomics, Medical Center Blvd, Winston-Salem, NC 27157. E-mail: jxu@wakehealth.edu, szheng@wakehealth.edu 1This work was supported by a National Cancer Institute RC2 grant (CA148463) and a research contract by GlaxoSmithKline (GSK) to J.X. L.D.C. and R.S.R. were GSK employees during this study and hold stock in GSK. J.G. is an employee of Hologic Gen-Probe, which supported PROGENSA PCA3 Assay testing under contractual agreement with GSK. J.X. certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), have been disclosed. 2This article refers to supplementary materials, which are designated by Tables W1 to W3 and Figures W1 to W3 and are available online at www.neoplasia.com. 3These authors contributed equally. Received 19 December 2012; Revised 6 February 2013; Accepted 7 February 2013 Copyright {\textcopyright} 2013 Neoplasia Press, Inc. All rights reserved 1522-8002/13/$25.00 DOI 10.1593/neo.122144",
year = "2013",
month = apr,
doi = "10.1593/neo.122144",
language = "English (US)",
volume = "15",
pages = "448--453",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "4",
}