Journal article

Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab

Hongyan Li, Bingjian Feng, Alexander Miron, Xiaoqing Chen, Jonathan Beesley, Emmanuella Bimeh, Daniel Barrowdale, Esther M John, Mary B Daly, Irene L Andrulis, Saundra S Buys, Peter Kraft, Heather Thorne, Georgia Chenevix-Trench, Melissa C Southey, Antonis C Antoniou, Paul A James, Mary Beth Terry, Kelly-Anne Phillips, John L Hopper Show all



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 ..

View full abstract


Awarded by Cancer Australia's Priority-driven Collaborative Cancer Research Scheme

Awarded by NIH

Awarded by NIH from the National Cancer Institute


Awarded by Cancer Research UK

Awarded by National Breast Cancer Foundation

Funding Acknowledgements

This research was supported by a grant from Cancer Australia's Priority-driven Collaborative Cancer Research Scheme no. 566791 (to G.M.) and by NIH grant U19 CA 148065-01 (DRIVE, part of the GAME-ON initiative) and NIH grant R01CA155767 (to D.E.G.). The Breast Cancer Family Registry is supported by NIH grants R01 CA159868 and UM1 CA164920 from the National Cancer Institute.r We thank Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the investigators and staff of the kConFab Clinical Follow-Up Study, which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the US National Institutes of Health, for their contributions to this resource. kConFab is supported by a grant from the National Breast Cancer Foundation and was previously supported by the National Health and Medical Research Council (NHMRC); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. Most importantly, the authors thank all the families enrolled in the BCFR and kConFab resources for their willingness to participate in research; without them, the work presented here would not be possible.