title: Common genetic variants in prostate cancer risk prediction--results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3).
abstract: BACKGROUND
  One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age.
  
  
  METHODS
  We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.
  
  
  RESULTS
  The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).
  
  
  CONCLUSIONS
  Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.
  
  
  CONCLUSIONS
  Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited.
authors.affiliation: Program in Molecular and Genetic Epidemiology,Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: David
authors.initials: D
authors.lastname: Cox
authors.forename: Ruth C
authors.initials: RC
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authors.forename: Demetrius
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authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Gerald
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authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Heiner
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authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Edward
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authors.lastname: Giovannucci
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Gonzalez
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Mattias
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authors.lastname: Johansson
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Jing
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authors.lastname: Ma
authors.forename: Loïc
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authors.lastname: Le Marchand
authors.forename: Valeria
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authors.lastname: Pala
authors.forename: Meir
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authors.lastname: Stampfer
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Meredith
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authors.lastname: Yeager
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Stephen J
authors.initials: SJ
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authors.forename: Peter
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authors.lastname: Kraft
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D016002:Discriminant Analysis; D055088:Early Detection of Cancer; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D054547:National Cancer Institute (U.S.); D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen