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The role of polygenic risk and susceptibility genes in breast cancer over the course of life

Author

Listed:
  • Nina Mars

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki)

  • Elisabeth Widén

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki)

  • Sini Kerminen

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki)

  • Tuomo Meretoja

    (Breast Surgery Unit, Comprehensive Cancer Center, Helsinki University Hospital
    University of Helsinki)

  • Matti Pirinen

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki
    University of Helsinki
    University of Helsinki)

  • Pietro della Briotta Parolo

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki)

  • Priit Palta

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki
    Institute of Genomics, University of Tartu)

  • Aarno Palotie

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki
    Massachusetts General Hospital
    Broad Institute of MIT and Harvard)

  • Jaakko Kaprio

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki
    University of Helsinki)

  • Heikki Joensuu

    (University of Helsinki
    Comprehensive Cancer Center, Helsinki University Hospital)

  • Mark Daly

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki
    Broad Institute of MIT and Harvard)

  • Samuli Ripatti

    (Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki
    University of Helsinki
    Broad Institute of MIT and Harvard)

Abstract

Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10–90th percentile) have a lifetime risk of breast cancer at 55% (95% CI 49–61%), which increases to 84% (71–97%) with a high PRS ( > 90th percentile), and decreases to 49% (30–68%) with a low PRS (

Suggested Citation

  • Nina Mars & Elisabeth Widén & Sini Kerminen & Tuomo Meretoja & Matti Pirinen & Pietro della Briotta Parolo & Priit Palta & Aarno Palotie & Jaakko Kaprio & Heikki Joensuu & Mark Daly & Samuli Ripatti, 2020. "The role of polygenic risk and susceptibility genes in breast cancer over the course of life," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19966-5
    DOI: 10.1038/s41467-020-19966-5
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    Cited by:

    1. Chen, Haidan, 2021. "Privacy in breast cancer biobank: Chinese patients’ perceptions," Social Science & Medicine, Elsevier, vol. 282(C).
    2. Chachrit Khunsriraksakul & Qinmengge Li & Havell Markus & Matthew T. Patrick & Renan Sauteraud & Daniel McGuire & Xingyan Wang & Chen Wang & Lida Wang & Siyuan Chen & Ganesh Shenoy & Bingshan Li & Xue, 2023. "Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Henrike O. Heyne & Fanny-Dhelia Pajuste & Julian Wanner & Jennifer I. Daniel Onwuchekwa & Reedik Mägi & Aarno Palotie & Reetta Kälviainen & Mark J. Daly, 2024. "Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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