RT Journal Article
SR Electronic
T1 Prevalence and clinical significance of pathogenic germline <em>BRCA1</em>/<em>2</em> mutations in Chinese non-small cell lung cancer patients
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 556
OP 564
DO 10.20892/j.issn.2095-3941.2018.0506
VO 16
IS 3
A1 Hu, Xingsheng
A1 Yang, Dongyong
A1 Li, Yalun
A1 Li, Li
A1 Wang, Yan
A1 Chen, Peng
A1 Xu, Song
A1 Pu, Xingxiang
A1 Zhu, Wei
A1 Deng, Pengbo
A1 Ye, Junyi
A1 Zhang, Hanhan
A1 Lizaso, Analyn
A1 Liu, Hao
A1 Mao, Xinru
A1 Huang, Hai
A1 Chu, Qian
A1 Hu, Chengping
YR 2019
UL http://www.cancerbiomed.org/content/16/3/556.abstract
AB 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.