Hemminki Kari, Sundquist Kristina, Sundquist Jan, Försti Asta, Liska Vaclav, Hemminki Akseli, Li Xinjun
Faculty of Medicine and Biomedical Center in Pilsen, Biomedical Center, Charles University in Prague, Pilsen.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Int J Cancer. 2023 Mar 15;152(6):1107-1114. doi: 10.1002/ijc.34308. Epub 2022 Oct 10.
Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.
已知许多肝胆癌的环境风险因素，但它们是否与特定癌症类型相关尚不清楚。我们在此提出一种新方法，用于评估先前诊断的肝细胞癌（HCC）、胆囊癌（GBC）、胆管癌（CCA）和壶腹癌的合并症标准化发病率（SIR）。这13种合并症包括酒精性和非酒精性肝病、慢性阻塞性肺疾病、胆结石病、病毒性肝炎和其他类型肝炎、胆管感染、肝脏和其他自身免疫性疾病、肥胖症和糖尿病。患者从1987年至2018年的瑞典住院患者登记册中识别出来，其癌症从1997年起进行随访。丙型肝炎病毒诊断患者中，HCC的SIR在男性和女性中为80至100，乙型肝炎病毒、其他类型肝炎、肝脏自身免疫性疾病和非酒精性肝病诊断患者的SIR也>10。这些风险中的许多，以及酒精性肝病，要么是HCC特有的，要么与肝内CCA共有。对于GBC、CCA和壶腹癌，胆管感染是主要风险因素。胆结石病、非肝脏自身免疫性疾病和糖尿病与所有肝胆癌相关。该研究的局限性包括无法涵盖一些罕见风险因素以及随访时间有限。许多所考虑的合并症的特征是慢性炎症和/或自身免疫性疾病中明显的免疫紊乱。结果表明，局部慢性炎症和相关免疫紊乱是所有这些癌症的致癌触发因素。
