Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

【Author】

Xingsheng Hu;Dongyong Yang;Yalun Li;Li Li;Yan Wang;Peng Chen;Song Xu;Xingxiang Pu;Wei Zhu;Pengbo Deng;Junyi Ye;Hanhan Zhang;Analyn Lizaso;Hao Liu;Xinru Mao;Hai Huang;Qian Chu;Chengping Hu;Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences;Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University;Department of Respiratory Medicine, West China Hospital, Sichuan University;Department of Respiratory Medicine, Daping Hospital;Department of Respiratory Medicine, Xinqiao Hospital,Army Medical University;Department of Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy,Tianjin; Tianjin's Clinical Research Center for Cancer;Department of Thoracic Oncology, Tianjin Medical University General Hospital;Department of Medical Oncology, Hunan Cancer Hospital;Department of Pathology, Xiangya Hospital, Central South University;Department of Respiratory Medicine, Xiangya Hospital, Central South University;Burning Rock Biotech;Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology;

【Institution】

Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences;Department of Pulmonary Medicine, Second Affiliated Hospital of Fujian Medical University;Department of Respiratory Medicine, West China Hospital, Sichuan University;Department of Respiratory Medicine, Daping Hospital;Department of Respiratory Medicine, Xinqiao Hospital,Army Medical University;Department of Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy,Tianjin; Tianjin's Clinical Research Center for Cancer;Department of Thoracic Oncology, Tianjin Medical University General Hospital;Department of Medical Oncology, Hunan Cancer Hospital;Department of Pathology, Xiangya Hospital, Central South University;Department of Respiratory Medicine, Xiangya Hospital, Central South University;Burning Rock Biotech;Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology;

【Abstract】

Objective: Germline alterations in the breast cancer susceptibility genes type 1 and 2, BRCA1 and BRCA2, predispose individuals to hereditary cancers, including breast, ovarian, prostate, pancreatic, and stomach cancers.Accumulating evidence suggests inherited genetic susceptibility to lung cancer.The present study aimed to survey the prevalence of pathogenic germline BRCA mutations(gBRCAm) and explore the potential association between gBRCAm and disease onset in Chinese advanced non-small cell lung cancer(NSCLC) patients.Methods: A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patients harboring germline BRCA1/2 mutations.Results: Out of the 6,220 patients screened, 1.03%(64/6,220) of the patients harbored the pathogenic gB RCAm, with BRCA2 mutations being the most predominant mutations(49/64, 76.5%).Patients who developed NSCLC before 50 years of age were more likely to carry gBRCAm(P = 0.036).Among the patients harboring classic lung cancer driver mutations, those with concurrent gBRCAm were significantly younger than those harboring the wild-type gBRCA(P = 0.029).By contrast, the age of patients with or without concurrent gBRCAm was comparable to those of patients without the driver mutations(P = 0.972).In addition, we identified EGFR-mutant patients with concurrent gBRCAm who showed comparable progression-free survival but significantly longer overall survival(P = 0.002) compared to EGFR-mutant patients with wild-type germline BRCA.Conclusions: Overall, our study is the largest survey of the prevalence of pathogenic gBRCAm in advanced Chinese NSCLC patients.Results suggested a lack of association between germline BRCA status and treatment outcome of EGFR-TKI.In addition,results showed a positive correlation between pathogenic gB RCAm and an early onset of NSCLC.

【Keywords】

Germline BRCA mutations;;non-small cell lung cancer;;prevalence;;BRCA1;;BRCA2

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