NEJM: Research on genetic assessment of breast cancer-related risks

Breast cancer high-risk genetic testing is beneficial for breast cancer screening, especially in high-risk groups such as family breast cancer history, but the evidence between many genes and breast cancer risk is weak, the potential risk assessment is not accurate, and there is a lack of reliable subtype-specific risk estimates.
Recently, researchers constructed a set of 34 suspected high-risk gene sequences, including protein truncation mutations and misalmutation mutations, sequenced 60,466 breast cancer patients and 53,461 control volunteers to assess the relationship between these risk genes and breast cancer risk.
study found that truncation mutations in ATMs, BRCA1, BRCA2, CHEK2 and PALB2, which cause early termination of protein transcription, were associated with an overall risk of breast cancer, with p-values of 0.000 1, while truncated mutations in the BARD1, RAD51C, RAD51D, and TP53 genes were associated with an overall risk of breast cancer, with P-values of 0.05 and Bayes error detection rates of 0.05.
the protein truncation mutations in 19 of the remaining 25 genes, the overall breast cancer advantage ratio was at the upper end of the 95% confidence interval.
For protein truncation mutations in the ATM and CHEK2 genes, the correlation with estrogen-positive breast cancer was higher than that of ER-negative breast cancer, and for protein truncation mutations in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, the correlation with ER-negative breast cancer was higher than that of ER-positive breast cancer.
, rare misalmed mutations in ATM, CHEK2, and TP53 were associated with breast cancer risk, with a P-value of 0.001.
mutations in the BRCA1, BRCA2, and TP53 genes, the risk was similar to that of protein truncation mutations.
the first time, the study defined the types of genetic mutations associated with clinical breast cancer risk, which is instructive in the assessment of breast cancer genetic risk.