Prevalence and clinical significance of pathogenic germline <i>BRCA1</i>/<i>2</i> mutations in Chinese non-small cell lung cancer patients
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | China Anti-Cancer Association 2019-09-01 |
Deskripsi
<b>Objective</b> Germline alterations in the breast cancer susceptibility genes type 1 and 2, <i>BRCA1</i> and <i>BRCA2</i>, 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 <i>BRCA</i> mutations (<i>gBRCAm</i>) and explore the potential association between <i>gBRCAm</i> and disease onset in Chinese advanced non-small cell lung cancer (NSCLC) patients.<b>Methods</b> A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patients harboring germline <i>BRCA1</i>/<i>2</i> mutations.<b>Results</b> Out of the 6,220 patients screened, 1.03% (64/6,220) of the patients harbored the pathogenic <i></i><i>g</i><i>BRCA</i><i>m</i><i></i>, with <i>BRCA2</i> mutations being the most pr<i></i><i></i>edominant mutations (49/64, 76.5%). Patients who developed NSCLC before 50 years of age were more likely to carry <i></i><i>g</i><i>BRCA</i><i>m</i><i></i> (<i>P</i> = 0.036). Among the patients harboring classic lung cancer driver mutations, those with concurrent <i></i><i>g</i><i>BRCA</i><i>m</i><i></i> were significantly younger than those harboring the wild-type <i></i><i>g</i><i>BRCA</i> (<i>P</i> = 0.029). By contrast, the age of patients with or without concurrent <i></i><i>g</i><i>BRCA</i><i>m</i><i></i> was comparable to those of patients without the driver mutations (<i>P</i> = 0.972). In addition, we identified<i></i> <i>EGFR</i>-mutant patients with concurrent g<i>BRCAm</i> who showed comparable progression-free survival but significantly longer overall survival (<i>P</i> = 0.002) compared to <i>EGFR</i>-mutant patients with wild-type germline <i>BRCA</i>.<b>Conclusions</b> Overall, our study is the largest survey of the prevalence of pathogenic <i></i><i>g</i><i>BRCA</i><i>m</i><i></i> in advanced Chinese NSCLC patients. Results suggested a lack of association between germline <i>BRCA</i> status and treatment outcome of EGFR-TKI. In addition, results showed a positive correlation between pathogenic <i></i><i>g</i><i>BRCA</i><i>m</i><i></i> and an early onset of NSCLC.