Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. While population-wide screening recommendations for PDAC in asymptomatic individuals are not achievable due to its relatively low incidence, pancreatic cancer surveillance programs are recommended for patients with germline causative variants in PDAC susceptibility genes or a strong family history. In this study, we sought to determine the prevalence and significance of germline alterations in major genes (ATM,BRCA1,BRCA2,CDKN2A,EPCAM,MLH1,MSH2,MSH6,PALB2,PMS2,STK11,TP53) involved in PDAC susceptibility. We performed a systematic review of PubMed publications reporting germline variants identified in these genes in PDAC patients. Overall, the retrieved articles included 1493 PDAC patients. A high proportion of these patients (n= 1225/1493, 82%) were found to harbor alterations in genes (ATM,BRCA1,BRCA2,PALB2) involved in the homologous recombination repair (HRR) pathway. Specifically, the remaining PDAC patients were reported to carry alterations in genes playing a role in other cancer pathways (CDKN2A,STK11,TP53;n= 181/1493, 12.1%) or in the mismatch repair (MMR) pathway (MLH1,MSH2,MSH6,PMS2;n= 87/1493, 5.8%). Our findings highlight the importance of germline genetic characterization in PDAC patients for better personalized targeted therapies, clinical management, and surveillance.
胰腺导管腺癌是全球致死率最高的恶性肿瘤之一。虽然因其发病率相对较低，目前无法对无症状人群实施全民筛查，但对于携带胰腺癌易感基因种系致病性变异或具有显著家族史的患者，建议参与胰腺癌监测计划。本研究旨在明确与胰腺癌易感相关主要基因（ATM、BRCA1、BRCA2、CDKN2A、EPCAM、MLH1、MSH2、MSH6、PALB2、PMS2、STK11、TP53）种系变异的流行率及其临床意义。我们系统检索了PubMed数据库中报道胰腺癌患者上述基因种系变异的研究文献。综合分析显示，纳入的1493例胰腺癌患者中，高达82%（1225/1493）携带同源重组修复通路相关基因（ATM、BRCA1、BRCA2、PALB2）变异。其余患者中，12.1%（181/1493）携带其他癌症通路相关基因（CDKN2A、STK11、TP53）变异，5.8%（87/1493）携带错配修复通路基因（MLH1、MSH2、MSH6、PMS2）变异。本研究结果凸显了胰腺癌患者种系基因特征分析对实施个体化靶向治疗、优化临床管理和监测策略的重要价值。
肿瘤(癌症)患者之家