title: Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer: Results from the prostate cancer prevention trial.
abstract: While family history (FH) has been widely used to provide risk information, it captures only a small proportion of subjects with higher genetic susceptibility. Our objective is to assess whether a genetic risk score (GRS) calculated from prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) can supplement FH for more effective risk stratification for PCa screening decision-making.
  
  
  
  A GRS was calculated based on 29 PCa risk-associated SNPs for 4,528 men of European descent in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). At study entry, participants were free of PCa diagnosis. Performance of FH and GRS were measured by observed detection rate of PCa and high-grade PCa (Gleason score ≥7) during the 7-year study.
  
  
  
  GRS was a significant predictor of PCa in men with or without a positive FH (P = 1.18 × 10(-4) and P = 4.50 × 10(-16) , respectively). Using FH alone, as expected, the 17% of men who were FH+ had a PCa detection rate that was significantly higher (29.02%) than FH- men (23.43%, P = 0.001). When both FH+ or GRS >1.4 are considered, more than twice as many men (36%) can be classified as higher risk, as evidenced by a significantly higher PCa detection rate (30.98%) than in the remaining men (20.61%, P = 5.30 × 10(-15) ). If targeting only FH+ men, four out of five PCa cases would go undetected, as would a similarly large fraction (∼80%) of high-grade PCa cases. In comparison, if targeting FH+ or GRS >1.4 men, almost half of all PCa cases would be detected, including 45% of high-grade PCa cases.
  
  
  
  A prostate cancer GRS can supplement family history to better identify higher risk men for targeted intervention. Prostate 76:1120-1129, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.|Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Haitao
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Brendler
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.|Departments of Mathematics and Life Sciences, Technical University Munich, Garching, Germany.
authors.forename: Donna P
authors.initials: DP
authors.lastname: Ankerst
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leach
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Goodman
authors.affiliation: University of Colorado Denver School of Medicine, Aurora, Colorado.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Tangen
authors.affiliation: Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.affiliation: Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Urology, UC San Diego Health System, San Diego, California.
authors.forename: A Karim
authors.initials: AK
authors.lastname: Kader
authors.affiliation: Department of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.affiliation: Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Department of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.|Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D060787:Neoplasm Grading; D010919:Placebos; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D044465:White People
chemical_list: D010919:Placebos
keywords: family history; prostate cancer; risk; single nucleotide polymorphisms; the prostate cancer prevention trial