NAT COMMUN: How does multigene risk affect the probability of breast cancer throughout life?

Breast cancer is the most common diagnosed cancer in women and the main cause of cancer-related deaths.
It is estimated that about 5-10% of breast cancers are developed due to mutations in the more affected lineages of the breast cancer susceptible gene, of which up to 30% are caused by pathogenic mutations in BRCA1 and BRCA2, and a small percentage are due to mutations carried by other susceptible genes such as PTEN, TP53, CHEK2, PALB2 and STK112.
Although disease-caused mutations in BRCA1 and BRCA2 are less common in Finns, the unique frequency of c.1592delT (rs180177102) in PALB2 and c.1100delC (rs555607708) in CHEK2 provides an opportunity to explore the unique effects of these mutations on populations.
risk score (PRS) for breast cancer has the potential to improve risk prediction, so far there has been limited information about its effectiveness in a variety of clinical situations.
recently, researchers published a paper in the journal Nature Communications showing that PRS modified the breast cancer risk of two high-impact shift-risk variants in 8,401 breast cancer cases among 122,978 women in the FinnGen study.
, the researchers showed that individuals with elevated PRS had an increased risk of lateral breast cancer after a breast cancer diagnosis, and that PRS significantly improved risk assessment for their female first-level relatives.
more detail, women with the c.1592delT variant in PALB2 (242 times rich in Finland, 336 carriers) had an average PRS (10-90th percentile) and a lifetime risk of breast cancer of 55 percent (95 percent CI 4 9-61%), however, if the PRS is high, the risk increases to 84% (71-97%), and if the PRS is low ( slt;10th percentile), the risk decreases to 49% (30-68%).
, for c.1100delC (3.7 times rich; 1,648 carriers) in CHEK2, the lifetime risks were 29% (27-32%), 59% (52-66%) and 9% (5-14%), respectively.
PRS also improves risk assessment for women diagnosed with breast cancer from a first-degree relative, especially those with a family history of early breast cancer positive.
, the study demonstrated the opportunity for a comprehensive assessment of genetic risk in the general population, breast cancer patients, and unaffected family members.
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