Objective: There are many hereditary breast cancer patients in China, and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives. However, the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women.Methods: We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls. These breast cancer patients were unselected for 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 high risk of breast cancer. ATM, BARD1, CHEK2, and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold. In contrast, pathogenic variants of NBN, RAD50, BRIP1, and RAD51C were not associated with increased risk of breast cancer in Chinese women. The pathogenic variants of PTEN, CDH1, and STK11 were very rare, so they had a limited contribution to Chinese breast cancer. Patients with pathogenic variants of TP53, BRCA1, BRCA2, and PALB2 more often had early-onset breast 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 genetic testing and clinical management of Chinese hereditary breast cancer.

Fenfen Fu;Dongjie Zhang;Li Hu;Senthil Sundaram;Dingge Ying;Ying Zhang;Shuna Fu;Juan Zhang;Lu Yao;Ye Xu;Yuntao Xie

Department of Breast Surgery,Peking University International Hospital,Beijing 102206,China;Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Familial&Hereditary Cancer Center,Peking University Cancer Hospital&Institute,Beijing 100142,China;Prenetics Limited,Hong Kong 999077,China;Beijing CircleDNA Gene Technology Co.,Ltd.,Beijing 100020,China

癌症生物学与医学（英文版）

[1]Fenfen Fu;Dongjie Zhang;Li Hu;Senthil Sundaram;Dingge Ying;Ying Zhang;Shuna Fu;Juan Zhang;Lu Yao;Ye Xu;Yuntao Xie-.Association between 15 known or potential breast cancersusceptibility genes and breast cancer risks in Chinese women)[J].癌症生物学与医学（英文版）,2022(02):253-262

cancersusceptibility,multigene,RAD51D,RAD51C

Association,between,potential,breast,genes,risks,Chinese,women,Objective,There,many,hereditary,patients,China,panel,testing,has,been,new,paradigm,genetic,these,their,relatives,However,magnitude,related,multiple,largely,unknown,Methods,We,screened,pathogenic,variants,established,from,consecutive,female,free,controls,These,were,unselected,diagnosis,family,history,Results,found,that,TP53,odds,ratio,confidence,interval,BRCA2,BRCA1,PALB2,associated,high,ATM,BARD1,CHEK2,moderate,ORs,ranging,fold,In,contrast,NBN,RAD50,BRIP1,not,increased,PTEN,CDH1,STK11,very,rare,they,had,limited,contribution,Patients,more,often,early,onset,bilateral,Conclusions,This,study,provided,assessment,data,which,useful,clinical,management

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