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Association between 15 known or potential breast cancer susceptibility genes and breast cancer risks in Chinese women

引用

cancer Biology & Medicine 2022年第2期19卷 253-262页

作者： 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 HospitalBeijing 102206China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Familial&Hereditary Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Prenetics Limited Hong Kong 999077China Beijing CircleDNA Gene Technology Co. Ltd.Beijing 100020China

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 earlyonset 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.

关键词： Multigene panel sequencing susceptibility genes breast cancer risk phenotype case-control study

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