title: The prostate cancer susceptibility variant rs2735839 near KLK3 gene is associated with aggressive prostate cancer and can stratify gleason score 7 patients.
abstract: OBJECTIVE
  Gleason score (GS) 7 prostate cancer is a heterogeneous disease with different clinical behavior. We sought to identify genetic biomarkers that may predict the aggressiveness of GS 7 diseases.
  
  
  METHODS
  We genotyped 72 prostate cancer susceptibility SNPs identified in genome-wide association studies in 1,827 white men with histologically confirmed prostate adenocarcinoma. SNPs associated with disease aggressiveness were identified by comparing high-aggressive (GS ≥8) and low-aggressive (GS ≤6) cases. The significant SNPs were then tested to see whether they could further stratify GS 7 prostate cancer.
  
  
  RESULTS
  Three SNPs-rs2735839, rs10486567, and rs103294-were associated with biopsy-proven high-aggressive (GS ≥8) prostate cancer (P < 0.05). Furthermore, the frequency of the variant allele (A) at rs2735839 was significantly higher in patients with biopsy-proven GS 4+3 disease than in those with GS 3 + 4 disease (P = 0.003). In multivariate logistic regression analysis, patients carrying the A allele at rs2735839 exhibited a 1.85-fold (95% confidence interval, 1.31-2.61) increased risk of being GS 4 + 3 compared with those with GS 3 + 4. The rs2735839 is located 600 base pair downstream of the KLK3 gene (encoding PSA) on 19q13.33 and has been shown to modulate PSA level, providing strong biologic plausibility for its association with prostate cancer aggressiveness.
  
  
  CONCLUSIONS
  We confirmed the association of the rs2735839 with high-aggressive prostate cancer (GS ≥8). Moreover, we reported for the first time that rs2735839 can stratify GS 7 patients, which would be clinically important for more accurately assessing the clinical behavior of the intermediate-grade prostate cancer and for tailoring personalized treatment and posttreatment management.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sara
authors.initials: S
authors.lastname: Strom
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jeri
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001706:Biopsy; D018450:Disease Progression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007610:Kallikreins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen