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. HopperGillian Mitchell, David E. Goldgar

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22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)30-35
Number of pages6
JournalGenetics in Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017
Externally publishedYes

Keywords

  • breast cancer
  • cancer screening
  • non-BRCA-Associated
  • polygenic risk score
  • risk prediction

Cite this

Li, H., Feng, B., Miron, A., Chen, X., Beesley, J., Bimeh, E., Barrowdale, D., John, E. M., Daly, M. B., Andrulis, I. L., Buys, S. S., Kraft, P., Thorne, H., Chenevix-Trench, G., Southey, M. C., Antoniou, A. C., James, P. A., Terry, M. B., Phillips, K. A., ... Goldgar, D. E. (2017). Breast cancer risk prediction using a polygenic risk score in the familial setting: a prospective study from the Breast Cancer Family Registry and kConFab. Genetics in Medicine, 19(1), 30-35. https://doi.org/10.1038/gim.2016.43