Hepatobiliary cancers (HBCs) include hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma, which originate from the liver, bile ducts, and gallbladder, respectively. They are responsible for a substantial burden of cancer-related deaths worldwide. Despite knowledge of risk factors and advancements in therapeutics and surgical interventions, the prognosis for most patients with HBC remains bleak. There is evidence from familial aggregation and case-control studies to suggest a familial risk component in HBC susceptibility. Recent progress in genomics research has led to the identification of germline variants including single nucleotide polymorphisms (SNPs) and pathogenic or likely pathogenic (P/LP) variants in cancer-associated genes associated with HBC risk. These findings emerged from genome-wide association studies and next-generation sequencing techniques such as whole-exome sequencing. Patients with other cancer types, including breast, colon, ovarian, prostate, and pancreatic cancer, are recommended by guidelines to undergo germline genetic testing, but similar recommendations are lagging in HBC. This prompts the question of whether multi-gene panel testing should be integrated into clinical guidelines for HBC management. Here, we review the hereditary genetics of HBC, explore studies investigating SNPs and P/LP variants in HBC patients, discuss the clinical implications and potential for personalized treatments and impact on patient’s family members, and conclude that additional studies are needed to examine how genetic testing can be applied clinically.

中文翻译：

---

肝胆癌的种系遗传关联

肝胆癌（HBC）包括肝细胞癌、胆管癌和胆囊癌，分别起源于肝脏、胆管和胆囊。他们对全世界癌症相关死亡负有重大责任。尽管对危险因素的了解以及治疗和手术干预方面的进步，大多数 HBC 患者的预后仍然黯淡。家族聚集和病例对照研究的证据表明，HBC 易感性存在家族风险因素。基因组学研究的最新进展导致了生殖系变异的鉴定，包括与 HBC 风险相关的癌症相关基因中的单核苷酸多态性 (SNP) 和致病性或可能致病性 (P/LP) 变异。这些发现来自全基因组关联研究和全外显子组测序等下一代测序技术。指南建议患有其他癌症类型（包括乳腺癌、结肠癌、卵巢癌、前列腺癌和胰腺癌）的患者接受种系基因检测，但类似的建议在 HBC 中却滞后。这就提出了一个问题：是否应将多基因面板检测纳入 HBC 管理的临床指南中。在这里，我们回顾了 HBC 的遗传遗传学，探索了调查 HBC 患者中 SNP 和 P/LP 变异的研究，讨论了个性化治疗的临床意义和潜力以及对患者家庭成员的影响，并得出结论，需要进行更多研究来检验遗传因素如何影响 HBC 的遗传性。测试可应用于临床。