title: Inherited genetic markers discovered to date are able to identify a significant number of men at considerably elevated risk for prostate cancer.
abstract: BACKGROUND
  Prostate cancer (PCa) risk-associated single-nucleotide polymorphisms (SNPs) are continuously being discovered. Their ability to identify men at high risk and the impact of increasing numbers of SNPs on predictive performance are not well understood.
  
  
  METHODS
  Absolute risk for PCa was estimated in a population-based case-control study in Sweden (2,899 cases and 1,722 controls) using family history and three sets of sequentially discovered PCa risk-associated SNPs. Their performance in predicting PCa was assessed by positive predictive values (PPV) and sensitivity.
  
  
  RESULTS
  SNPs and family history were able to differentiate individual risk for PCa and identify men at higher risk; ∼18% and ∼8% of men in the study had 20-year (55-74 years) absolute risks that were twofold (0.24) or threefold (0.36) greater than the population median risk (0.12), respectively. When predictive performances were compared at absolute risk cutoffs of 0.12, 0.24, or 0.36, PPV increased considerably (∼20%, ∼30%, and ∼37%, respectively) while sensitivity decreased considerably (∼55%, ∼20%, and ∼10%, respectively). In contrast, when increasing numbers of SNPs (5, 11, and 28 SNPs) were used in risk prediction, PPV approached a constant value while sensitivity increased steadily.
  
  
  CONCLUSIONS
  SNPs discovered to date are suitable for risk prediction while additional SNPs discovered in the future may identify more subjects at higher risk. Men identified as high risk by SNP-based testing may be targeted for PCa screening or chemoprevention. The clinical impact on improving the effectiveness of these interventions can be and should be assessed.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: A Karim
authors.initials: AK
authors.lastname: Kader
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Aubrey R
authors.initials: AR
authors.lastname: Turner
authors.forename: Tao
authors.initials: T
authors.lastname: Jin
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jan
authors.initials: J
authors.lastname: Adolfsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D012306:Risk
chemical_list: D005819:Genetic Markers