title: Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab.
abstract: This study examined the utility of sets of single-nucleotide polymorphisms (SNPs) in familial but non-BRCA-associated breast cancer (BC).
  
  
  
  We derived a polygenic risk score (PRS) based on 24 known BC risk SNPs for 4,365 women from the Breast Cancer Family Registry and Kathleen Cuningham Consortium Foundation for Research into Familial Breast Cancer familial BC cohorts. We compared scores for women based on cancer status at baseline; 2,599 women unaffected at enrollment were followed-up for an average of 7.4 years. Cox proportional hazards regression was used to analyze the association of PRS with BC risk. The BOADICEA risk prediction algorithm was used to measure risk based on family history alone.
  
  
  
  The mean PRS at baseline was 2.25 (SD, 0.35) for affected women and was 2.17 (SD, 0.35) for unaffected women from combined cohorts (P < 10-6). During follow-up, 205 BC cases occurred. The hazard ratios for continuous PRS (per SD) and upper versus lower quintiles were 1.38 (95% confidence interval: 1.22-1.56) and 3.18 (95% confidence interval: 1.84-5.23) respectively. Based on their PRS-based predicted risk, management for up to 23% of women could be altered.
  
  
  
  Including BC-associated SNPs in risk assessment can provide more accurate risk prediction than family history alone and can influence recommendations for cancer screening and prevention modalities for high-risk women.Genet Med 19 1, 30-35.
authors.affiliation: Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Bingjian
authors.initials: B
authors.lastname: Feng
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts, USA.|Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Jonathan
authors.identifier: 0000-0003-1942-325X
authors.initials: J
authors.lastname: Beesley
authors.affiliation: Division of Family and Preventive Medicine, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Emmanuella
authors.initials: E
authors.lastname: Bimeh
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Daniel
authors.identifier: 0000-0003-1661-3939
authors.initials: D
authors.lastname: Barrowdale
authors.affiliation: Cancer Prevention Institute of California, Fremont, California, USA.|Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.affiliation: Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Department of Molecular Genetics, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
authors.affiliation: Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Buys
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Research Division, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: Heather
authors.initials: H
authors.lastname: Thorne
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
authors.forename: Melissa C
authors.identifier: 0000-0002-6313-9005
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.affiliation: Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Paul A
authors.identifier: 0000-0002-4361-4657
authors.initials: PA
authors.lastname: James
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.affiliation: Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.|Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
authors.affiliation: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: John L
authors.identifier: 0000-0002-8567-173X
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.affiliation: Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.|Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: David E
authors.identifier: 0000-0003-0697-9347
authors.initials: DE
authors.lastname: Goldgar
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020412:Multifactorial Inheritance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors