Association Between 15 Known or Potential Breast Cancer Susceptibility Genes and Breast Cancer Risks in Chinese Women

Objective: There are many hereditary breast cancer patients in China, and multigene panel testing has been a new paradigm ofgenetic testing for these patients and their relatives. However, the magnitude of breast cancer risks related to multiple breast cancersusceptibility genes are largely unknown in Chinese women. Methods: We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutiveChinese female breast cancer patients and 13,129 Chinese cancer-free female controls. These breast cancer patients were unselectedfor age at diagnosis or family history. Results: We found that pathogenic variants in TP53 [odds ratio (OR): 16.9, 95% confidence interval (CI): 5.2–55.2]; BRCA2 (OR:10.4, 95% CI: 7.6–14.2); BRCA1 (OR: 9.7, 95% CI: 6.3–14.8); and PALB2 (OR: 5.2, 95% CI: 3.0–8.8) were associated with a highrisk of breast cancer. ATM, BARD1, CHEK2, and RAD51D were associated with a moderate risk of breast cancer with ORs rangingfrom 2-fold to 4-fold. In contrast, pathogenic variants of NBN, RAD50, BRIP1, and RAD51C were not associated with increasedrisk of breast cancer in Chinese women. The pathogenic variants of PTEN, CDH1, and STK11 were very rare, so they had a limitedcontribution to Chinese breast cancer. Patients with pathogenic variants of TP53, BRCA1, BRCA2, and PALB2 more often had earlyonsetbreast cancer, bilateral breast cancer, and a family history of breast cancer and/or any cancer. Conclusions: This study provided breast cancer risk assessment data for multiple genes in Chinese women, which is useful for genetictesting and clinical management of Chinese hereditary breast cancer.