Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, China.
Department of Radiotherapy, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China.
Int J Cancer. 2019 Sep 15;145(6):1517-1528. doi: 10.1002/ijc.32184. Epub 2019 Feb 22.
To gain more information on the prevalence of germline mutations in BRCA1/2 and PALB2 genes in the Chinese population, and to explore the effects of the mutation status of these genes on clinical outcomes in patients with breast cancer, we performed a screening for BRCA1/2 and PALB2 mutations in a consecutive series of unselected breast cancer patients in the Chinese population. A total of 2,769 cases were enrolled between June 1993 and September 2017. All of the exons and exon-intron boundaries of the BRCA1/2 and PALB2 genes were screened with next-generation sequencing. Of the 2,769 breast cancer patients, BRCA1, BRCA2 and PALB2 mutations accounted for 2.7% (n = 74), 2.7% (n = 76), and 0.9% (n = 24), respectively. The BRCA1 gene had the highest mutation frequency in patients with triple-negative breast cancer (TNBC), which was 9.6% (n = 42), while the BRCA2 gene had the highest mutation frequency in patients with Luminal, which was 3.2% (n = 58). The disease-free survival (DFS) of BRCA1 mutation carriers was significantly lower than that of noncarriers (adjusted HR = 2.20, 95% CI = 1.15-4.18, p = 0.017). The mutation status of the PALB2 gene was significantly associated with the decline in overall survival (OS) (adjusted HR = 8.38, 95% CI = 2.19-32.11, p = 0.002). No significant difference was found between BRCA2 pathogenic mutation carriers and noncarriers. These results demonstrate that BRCA1 mutation status may be associated with a worse disease progression in patients with breast cancer, and women who harbored a PALB2 mutation might be at a higher risk of death due to breast cancer compared to noncarriers.
为了获取更多关于中国人群中 BRCA1/2 和 PALB2 基因种系突变的流行情况，并探讨这些基因突变状态对乳腺癌患者临床结局的影响，我们对中国人群中连续的未选择的乳腺癌患者进行了 BRCA1/2 和 PALB2 基因突变筛查。共纳入 1993 年 6 月至 2017 年 9 月期间的 2769 例病例。采用下一代测序法对 BRCA1/2 和 PALB2 基因的所有外显子和外显子-内含子边界进行了筛选。在 2769 例乳腺癌患者中，BRCA1、BRCA2 和 PALB2 基因突变的比例分别为 2.7%（n=74）、2.7%（n=76）和 0.9%（n=24）。BRCA1 基因突变在三阴性乳腺癌（TNBC）患者中频率最高，为 9.6%（n=42），而 BRCA2 基因突变在 Luminal 型乳腺癌患者中频率最高，为 3.2%（n=58）。BRCA1 基因突变携带者的无病生存（DFS）显著低于非携带者（调整 HR=2.20，95%CI=1.15-4.18，p=0.017）。PALB2 基因突变状态与总生存（OS）下降显著相关（调整 HR=8.38，95%CI=2.19-32.11，p=0.002）。BRCA2 致病性基因突变携带者与非携带者之间无显著差异。这些结果表明，BRCA1 基因突变状态可能与乳腺癌患者疾病进展恶化相关，与非携带者相比，携带 PALB2 突变的女性可能因乳腺癌死亡的风险更高。
