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How do #breastcancer susceptibility genes, polygenic risk score (PRS) and family history impact the risk of breast cancer over the life course?
With @ninjmars, we tested this in @FinnGen_FI in 120,000 women:
https://www.nature.com/articles/s41467-020-19966-5
@NatureComms @fimm_uh @CoECDG
With @ninjmars, we tested this in @FinnGen_FI in 120,000 women:
https://www.nature.com/articles/s41467-020-19966-5
@NatureComms @fimm_uh @CoECDG
First, we developed a new genome-wide PRS, which outperformed previously published PRSs.
In line with previous studies on breast cancer and several other common diseases, genome-wide scores outperformed PRSs containing a smaller number of variants.
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In line with previous studies on breast cancer and several other common diseases, genome-wide scores outperformed PRSs containing a smaller number of variants.
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We took carriers of two important frameshift variants in PALB2 and CHEK2 and compared their lifetime risks with women in the top decile of the polygenic risk score.
Women with a high PRS had a lifetime risk of 33%, at least similar to that conferred by CHEK2.
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Women with a high PRS had a lifetime risk of 33%, at least similar to that conferred by CHEK2.
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The relative risks for the PRS were similar in mutation carriers and in non-carriers. The PRS modified the risk considerably in both CHEK2 and PALB2 mutation carriers, e.g. CHEK2 and a PRS in the protective tail conferred a lifetime risk lower than the population average.
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We show that women diagnosed with breast cancer who have a PRS in the top decile had a 1.6-fold elevated risk for contralateral breast cancer. Moreover, we show that PRS could considerably improve breast cancer risk assessment of their first-degree relatives.
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Our study highlights opportunities arising from comprehensive assessment of genetic risk in the population, in breast cancer patients, and in unaffected family members.
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The work was done by a terrific team @ninajmars, Elisabeth Widén, @SiniKerminen, Tuomo Meretoja, @APalotie, @JKaprio, Heikki Joensuu, @dalygene and many others.
We are grateful for the amazing @FinnGen_FI community, the biobanks, Finns who have donated samples.
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We are grateful for the amazing @FinnGen_FI community, the biobanks, Finns who have donated samples.
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Apologies, the correct Twitter handle for Nina Mars is of course @ninajmars. Now go follow her.
