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Li H , Feng B , Miron A , Chen X , Beesley J , Bimeh E , Barrowdale D , John EM , Daly MB , Andrulis IL , Buys SS , Kraft P , Thorne H , Chenevix-Trench G , Southey MC , Antoniou AC , James PA , Terry MB , Phillips KA , Hopper JL , Mitchell G , Goldgar DE
Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab
Genet Med. 2017 Jan;19(1) :30-35
PMID: 27171545    PMCID: PMC5107177   
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PURPOSE: This study examined the utility of sets of single-nucleotide polymorphisms (SNPs) in familial but non-BRCA-associated breast cancer (BC). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
1530-0366 Li, Hongyan Feng, Bingjian Miron, Alexander Chen, Xiaoqing Beesley, Jonathan Orcid: 0000-0003-1942-325x Bimeh, Emmanuella Barrowdale, Daniel Orcid: 0000-0003-1661-3939 John, Esther M Daly, Mary B Andrulis, Irene L Buys, Saundra S Kraft, Peter kConFab investigators Thorne, Heather Chenevix-Trench, Georgia Southey, Melissa C Orcid: 0000-0002-6313-9005 Antoniou, Antonis C James, Paul A Orcid: 0000-0002-4361-4657 Terry, Mary Beth Phillips, Kelly-Anne Hopper, John L Orcid: 0000-0002-8567-173x Mitchell, Gillian Goldgar, David E Orcid: 0000-0003-0697-9347 R01 CA155767/CA/NCI NIH HHS/United States R35 CA197449/CA/NCI NIH HHS/United States UM1 CA164920/CA/NCI NIH HHS/United States R01 CA159868/CA/NCI NIH HHS/United States U19 CA148065/CA/NCI NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Genet Med. 2017 Jan;19(1):30-35. doi: 10.1038/gim.2016.43. Epub 2016 May 12.