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

Nina Mars; Elisabeth Widen; Tuomo Meretoja; Sini Kerminen; Matti Pirinen; Pietro Della Briotta Parolo; Priit Palta; FinnGen; Aarno Palotie; Jaakko Kaprio; Heikki Joensuu; Mark Daly; Samuli Ripatti; Kalle Pärn; Pentti Tienari

doi:10.1038/s41467-020-19966-5

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

Nina Mars, Elisabeth Widen, Tuomo Meretoja, Sini Kerminen, Matti Pirinen, Pietro Della Briotta Parolo, Priit Palta, FinnGen, Aarno Palotie, Jaakko Kaprio, Heikki Joensuu, Mark Daly, Samuli Ripatti, Kalle Pärn, Pentti Tienari

Research output: Contribution to journal › Article › Scientific › peer-review

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 (10-90(th) percentile) have a lifetime risk of breast cancer at 55% (95% CI 49-61%), which increases to 84% (71-97%) with a high PRS (>90(th) percentile), and decreases to 49% (30-68%) with a low PRS (

Original language	English
Article number	6383
Journal	Nature Communications
Volume	11
Issue number	1
Number of pages	9
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-020-19966-5
Publication status	Published - 14 Dec 2020
MoE publication type	A1 Journal article-refereed

Fields of Science

3122 Cancers
MUTATIONS
FAMILIES
BRCA2
WOMEN

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Cite this

Mars, N., Widen, E., Meretoja, T., Kerminen, S., Pirinen, M., Della Briotta Parolo, P., Palta, P., FinnGen, Palotie, A., Kaprio, J., Joensuu, H., Daly, M., Ripatti, S., Pärn, K., & Tienari, P. (2020). The role of polygenic risk and susceptibility genes in breast cancer over the course of life. Nature Communications, 11(1), Article 6383. https://doi.org/10.1038/s41467-020-19966-5

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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 (10-90(th) percentile) have a lifetime risk of breast cancer at 55% (95% CI 49-61%), which increases to 84% (71-97%) with a high PRS (>90(th) percentile), and decreases to 49% (30-68%) with a low PRS (",

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AU - Widen, Elisabeth

AU - Meretoja, Tuomo

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AU - Pirinen, Matti

AU - Della Briotta Parolo, Pietro

AU - Palta, Priit

AU - FinnGen

AU - Palotie, Aarno

AU - Kaprio, Jaakko

AU - Joensuu, Heikki

AU - Daly, Mark

AU - Ripatti, Samuli

AU - Pärn, Kalle

AU - Tienari, Pentti

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N2 - 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 (10-90(th) percentile) have a lifetime risk of breast cancer at 55% (95% CI 49-61%), which increases to 84% (71-97%) with a high PRS (>90(th) percentile), and decreases to 49% (30-68%) with a low PRS (

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