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 x 10(-9) and 1.06 x 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.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Jack
authors.initials: J
authors.lastname: Groskopf
authors.forename: Junjie
authors.initials: J
authors.lastname: Feng
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Roger S
authors.initials: RS
authors.lastname: Rittmaster
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Condreay
authors.forename: Siqun Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics / Q000652:urine*; D029584:Prostatic Secretory Proteins / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D017422:Sequence Analysis, DNA; D020840:Tissue Kallikreins / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C479341:prostate cancer antigen 3, human; D020840:Tissue Kallikreins
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