Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline genetic testing in all patients with PDAC. Methods: Individuals with newly diagnosed PDAC from three Spanish hospitals were enrolled, regardless of family history. Thirteen known susceptibility genes for PDAC were studied using a multigene panel or whole-exome sequencing. Results: One hundred seventy-nine PDAC patients underwent genetic testing. Fourteen (7.8%) had a GPV or likely pathogenic variant In the genes studied: six inATM, six inBRCA2, one inPALB2, and one inTP53. Of these, seven (50%) did not meet the clinical criteria for genetic study and would have been classified as sporadic PDAC. Presenting with a personal history of any other neoplasm was associated with some GPV, with an odds ratio (OR) of 3.5 (1.1–11.5). A family history of PDAC and breast cancer was also associated with some GPV, with oRs of 3.7 (1.08–13.6) and 8.5 (2.6–26.6), respectively. None of the patients over 60 years without a relevant family history of malignancies presented a GPV associated with PDAC. Conclusions: In our PDAC cohort, a noteworthy number of GPVs were identified, and half of these patients would have been classified as sporadic based solely on clinical criteria. Genetic testing should always be considered, particularly in patients under 60 years or those with a history of other malignancies, especially where economic resources need optimization.
背景：胰腺导管腺癌（PDAC）与相当比例的胚系致病性变异（GPV）相关。与美国不同，欧洲并未常规开展普适性基因检测。本研究旨在评估对所有PDAC患者进行胚系基因检测的诊断效能。方法：纳入西班牙三家医院新诊断的PDAC患者，无论其家族史如何。采用多基因组合检测或全外显子组测序技术，对13个已知的PDAC易感基因进行分析。结果：179例PDAC患者接受了基因检测。其中14例（7.8%）在所研究基因中发现GPV或可能致病性变异：ATM基因6例，BRCA2基因6例，PALB2基因1例，TP53基因1例。在这些携带变异的患者中，7例（50%）不符合基因检测的临床标准，若仅依据临床标准会被归类为散发性PDAC。携带其他任何肿瘤个人史与存在GPV相关，比值比（OR）为3.5（1.1–11.5）。PDAC和乳腺癌家族史也与存在GPV相关，OR值分别为3.7（1.08–13.6）和8.5（2.6–26.6）。在年龄超过60岁且无相关恶性肿瘤家族史的患者中，未发现与PDAC相关的GPV。结论：在我们的PDAC队列中，发现了相当数量的GPV，其中半数患者若仅依据临床标准会被归类为散发性病例。应始终考虑进行基因检测，特别是对于60岁以下患者或有其他恶性肿瘤病史的患者，在需要优化经济资源配置的情况下尤其如此。
肿瘤(癌症)患者之家