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

Tutkimustuotos: Artikkelijulkaisu › Artikkeli › Tieteellinen › vertaisarvioitu

Abstrakti

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 (

Alkuperäiskieli	englanti
Artikkeli	6383
Lehti	Nature Communications
Vuosikerta	11
Numero	1
Sivumäärä	9
ISSN	2041-1723
DOI - pysyväislinkit	https://doi.org/10.1038/s41467-020-19966-5
Tila	Julkaistu - 14 jouluk. 2020
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

3122 Syöpätaudit

Pääsy asiakirjaan

10.1038/s41467-020-19966-5Lisenssi: CC BY

s41467-020-19966-5Lopullinen julkaistu versio, 2,87 MBLisenssi: CC BY

Siteeraa tätä

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), [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 (",

keywords = "3122 Cancers, MUTATIONS, FAMILIES, BRCA2, WOMEN",

author = "Nina Mars and Elisabeth Widen and Tuomo Meretoja and Sini Kerminen and Matti Pirinen and {Della Briotta Parolo}, Pietro and Priit Palta and FinnGen and Aarno Palotie and Jaakko Kaprio and Heikki Joensuu and Mark Daly and Samuli Ripatti and Kalle P{\"a}rn and Pentti Tienari",

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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, Vuosikerta 11, Nro 1, 6383. https://doi.org/10.1038/s41467-020-19966-5

TY - JOUR

T1 - The role of polygenic risk and susceptibility genes in breast cancer over the course of life

AU - Mars, Nina

AU - Widen, Elisabeth

AU - Meretoja, Tuomo

AU - Kerminen, Sini

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

PY - 2020/12/14

Y1 - 2020/12/14

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 (

AB - 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 (

KW - 3122 Cancers

KW - MUTATIONS

KW - FAMILIES

KW - BRCA2

KW - WOMEN

U2 - 10.1038/s41467-020-19966-5

DO - 10.1038/s41467-020-19966-5

M3 - Article

VL - 11

JO - Nature Communications

JF - Nature Communications

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