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

Xingsheng Hu, Dongyong Yang, Yalun Li, et al


Objective: Germline alterations in the breast cancer susceptibility genes type 1 and 2, BRCA1 and BRCA2, predispose individualsto hereditary cancers, including breast, ovarian, prostate, pancreatic, and stomach cancers. Accumulating evidence suggestsinherited genetic susceptibility to lung cancer. The present study aimed to survey the prevalence of pathogenic germline BRCAmutations (gBRCAm) and explore the potential association between gBRCAm and disease onset in Chinese advanced non-smallcell lung cancer (NSCLC) patients.

Methods: A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patientsharboring 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 BRCA2mutations being the most predominant mutations (49/64, 76.5%). Patients who developed NSCLC before 50 years of age weremore likely to carry gBRCAm (P = 0.036). Among the patients harboring classic lung cancer driver mutations, those withconcurrent gBRCAm were significantly younger than those harboring the wild-type gBRCA (P = 0.029). By contrast, the age ofpatients with or without concurrent gBRCAm was comparable to those of patients without the driver mutations (P = 0.972). Inaddition, we identified EGFR-mutant patients with concurrent gBRCAm who showed comparable progression-free survival butsignificantly 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 NSCLCpatients. 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.


Cite this article as: Hu X, Yang D, Li Y, Li L, Wang Y, Chen P, et al.Prevalence and clinical significance of pathogenic germline BRCA1/2mutations in Chinese non-small cell lung cancer patients. Cancer Biol Med.2019; 16: 556-64. doi: 10.20892/j.issn.2095-3941.2018.0506


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

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