title: New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort.
abstract: OBJECTIVE
  To identify and examine polymorphisms of genes associated with aggressive and clinical significant forms of prostate cancer among a screening cohort.
  
  
  METHODS
  We conducted a genome-wide association study among patients with aggressive forms of prostate cancer and biopsy-proven normal controls ascertained from a prostate cancer screening program. We then examined significant associations of specific polymorphisms among a prostate cancer screened cohort to examine their predictive ability in detecting prostate cancer.
  
  
  RESULTS
  We found significant associations between aggressive prostate cancer and five single nucleotide polymorphisms (SNPs) in the 10q26 (rs10788165, rs10749408, and rs10788165, p value for association 1.3 × 10(-10 ) to 3.2 × 10(-11) ) and 15q21 (rs4775302 and rs1994198, p values for association 3.1 × 10(-8 ) to 8.2 × 10(-9)) regions. Results of a replication study done in 3439 patients undergoing a prostate biopsy, revealed certain combinations of these SNPs to be significantly associated not only with prostate cancer but with aggressive forms of prostate cancer using an established classification criterion for prostate cancer progression (odds ratios for intermediate to high-risk disease 1.8-3.0, p value 0.003-0.001). These SNP combinations were also important clinical predictors for prostate cancer detection based on nomogram analysis that assesses prostate cancer risk.
  
  
  CONCLUSIONS
  Five SNPs were found to be associated with aggressive forms of prostate cancer. We demonstrated potential clinical applications of these associations.
authors: Division of Urology, Sunnybrook Research Institute, University of Toronto, ON, Canada. robert.nam@utoronto.ca
authors: Robert K
authors: RK
authors: Nam
authors: William
authors: W
authors: Zhang
authors: Katherine
authors: K
authors: Siminovitch
authors: Adam
authors: A
authors: Shlien
authors: Michael W
authors: MW
authors: Kattan
authors: Laurence H
authors: LH
authors: Klotz
authors: John
authors: J
authors: Trachtenberg
authors: Yan
authors: Y
authors: Lu
authors: Jinyi
authors: J
authors: Zhang
authors: Changhong
authors: C
authors: Yu
authors: Ants
authors: A
authors: Toi
authors: D Andrew
authors: DA
authors: Loblaw
authors: Vasundara
authors: V
authors: Venkateswaran
authors: Aleksandra
authors: A
authors: Stanimirovic
authors: Linda
authors: L
authors: Sugar
authors: David
authors: D
authors: Malkin
authors: Arun
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authors: Seth
authors: Steven A
authors: SA
authors: Narod
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001706:Biopsy; D002879:Chromosomes, Human, Pair 10; D002884:Chromosomes, Human, Pair 15; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity