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

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收录情况: ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C

单位: [1]Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100021, Peoples R China [2]Fujian Med Univ, Affiliated Hosp 2, Dept Pulm Med, Quanzhou 362100, Fujian, Peoples R China [3]Sichuan Univ, West China Hosp, Dept Resp Med, Chengdu 610041, Sichuan, Peoples R China [4]Daping Hosp, Dept Resp Med, Chongqing 400042, Peoples R China [5]Army Med Univ, Xinqiao Hosp, Dept Resp Med, Chongqing 400037, Peoples R China [6]Tianjin Med Univ Canc Inst & Hosp, Key Lab Canc Prevent & Therapy, Natl Clin Res Ctr Canc, Dept Med Oncol, Tianjin, Peoples R China [7]Tianjins Clin Res Ctr Canc, Tianjin 300060, Peoples R China [8]Tianjin Med Univ, Dept Thorac Oncol, Gen Hosp, Tianjin 300052, Peoples R China [9]Hunan Canc Hosp, Dept Med Oncol, Changsha 410006, Hunan, Peoples R China [10]Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha 410008, Hunan, Peoples R China [11]Cent S Univ, Xiangya Hosp, Dept Resp Med, Changsha 410008, Hunan, Peoples R China [12]Burning Rock Biotech, Guangzhou 510300, Guangdong, Peoples R China [13]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Oncol, Wuhan 430022, Hubei, Peoples R China
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关键词: Germline BRCA mutations non-small cell lung cancer prevalence BRCA1 BRCA2

摘要:
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 gBRCAm, 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 gBRCAm and an early onset of NSCLC.

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出版当年[2018]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 3 区 肿瘤学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 2 区 肿瘤学
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出版当年[2017]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q2 ONCOLOGY
最新[2023]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者单位: [1]Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing 100021, Peoples R China
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