如果没有显着的癌症家族史，通常不会怀疑遗传性癌症易感性。胰腺癌的致病种系变异已得到充分研究，指南中建议进行常规基因检测。然而，关于胰腺癌以外的罕见壶腹周围癌症的数据不足。我们比较了胰腺癌和非胰腺壶腹周围癌患者种系易感性变异的发生率。 研究对象为三级转诊医院接受胰十二指肠切除术的 608 例患者，其中胰腺导管腺癌 213 例，壶腹癌 172 例，胰十二指肠癌 154 例。远端胆总管癌 69 例，十二指肠腺癌 69 例。对 20 个癌症易感性和候选易感性基因进行了测序，并通过询问 ClinVar 和 PubMed 评估了变异解释。在 46 名患者 (7.7%) 中发现了致病性或可能致病性、中度至高渗透性种系变异，其中包括相似比例的患者胰腺癌（8.5%）和非胰腺壶腹周围癌（7.1%）。另外 11 名患者 (1.8%) 中发现了低渗透变异。 89% 的中度至高渗透性变异涉及主要癌症易感基因 BRCA2、ATM、BRCA1、CDKN2A、MSH2/MLH1 和 PALB2；其余11%涉及其他癌症易感基因，如BRIP1、BAP1和MSH6。几乎所有致病性变异携带者都有癌症家族史。胰腺和非胰腺壶腹周围癌患者的致病性癌症易感性变异的患病率相似。对于任何壶腹周围癌患者都应考虑进行种系敏感性检测。

Inherited cancer susceptibility is often not suspected in the absence of a significant cancer family history. Pathogenic germline variants in pancreatic cancer are well-studied, and routine genetic testing is recommended in the guidelines. However, data on rare periampullary cancers other than pancreatic cancer are insufficient. We compared the prevalence of germline susceptibility variants in patients with pancreatic cancer and nonpancreatic periampullary cancers.Six hundred and eight patients who had undergone pancreaticoduodenal resection at a tertiary referral hospital were studied, including 213 with pancreatic ductal adenocarcinoma, 172 with ampullary cancer, 154 with distal common bile duct cancer, and 69 with duodenal adenocarcinoma. Twenty cancer susceptibility and candidate susceptibility genes were sequenced, and variant interpretation was assessed by interrogating ClinVar and PubMed.Pathogenic or likely pathogenic, moderate- to high-penetrant germline variants were identified in 46 patients (7.7%), including a similar percentage of patients with pancreatic (8.5%) and nonpancreatic periampullary cancer (7.1%). Low-penetrant variants were identified in an additional 11 patients (1.8%). Eighty-nine percent of the moderate- to high-penetrant variants involved the major cancer susceptibility genes BRCA2, ATM, BRCA1, CDKN2A, MSH2/MLH1, and PALB2; the remaining 11% involved other cancer susceptibility genes such as BRIP1, BAP1, and MSH6. Almost all pathogenic variant carriers had a family history of cancer.Patients with pancreatic and nonpancreatic periampullary cancer have a similar prevalence of pathogenic cancer susceptibility variants. Germline susceptibility testing should be considered for patients with any periampullary cancer.