Personal comorbidities and their subsequent risks for liver, gallbladder and bile duct cancers

Abstract

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.

The footprint of gut microbiota in gallbladder cancer: a mechanistic review

“…Appropriate immune responses eliminate pathogens that are detrimental to organisms, but prolonged immune responses result in chronic inflammation, local tissue damage and even cancer ( Bucciantini et al., 2021 ). Analyzing the relationship between 13 personal comorbidities and the risk of subsequent GBC, a recent study indicated that infection is a major risk factor for GBC, while local chronic inflammation and associated immune disorders are carcinogenic triggers ( Hemminki et al., 2023 ), regardless of whether its origin is lithological or not ( Cai et al., 2023 ). There may be multiple carcinogenic mechanisms involved, with common characteristics in changed signaling pathways and increased inflammatory factors ( Rubini et al., 2018 ).…”

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis

“…Moreover, many HBCs are diagnosed at advanced stages, which exacerbates the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent for the prevention of HBC. Several risk factors, including alcohol consumption, viral hepatitis, and non-alcoholic fatty liver disease (NAFLD), have been identified as important triggers for the development of HCC ( 5 ) In BTC, metabolism, obesity-related characteristics and hepatobiliary disease are the common risk factors ( 6 ). However, there are still around 20% of HCC patients and 50% of BTC patients are diagnosed without any identifiable risk factors ( 6 , 7 ).…”

Autoimmune diseases as comorbidities for liver, gallbladder, and biliary duct cancers in Sweden

“…Hepatobiliary cancers include hepatocellular carcinoma (HCC), biliary tract cholangiocarcinoma (CCA), gallbladder cancer (GBC), and cancer of the ampulla of Vater (ampullary cancer) 1,2 . The large international variation in the incidence of these cancers can be explained by the differential distribution of known risk factors, which for HCC include chronic infection by hepatitis B (HBV) or hepatitis C virus (HCV) in developing countries, and alcohol, other lifestyle factors, and family history in developed countries 1–5 . Since 2009, Sweden has had a national HCC register reporting what the causes for HCC were ascribed to: HCV in 30%, alcohol in 25%, and HBV in 6% of the patients 6 .…”

“…1,2 The large international variation in the incidence of these cancers can be explained by the differential distribution of known risk factors, which for HCC include chronic infection by hepatitis B (HBV) or hepatitis C virus (HCV) in developing countries, and alcohol, other lifestyle factors, and family history in developed countries. [1][2][3][4][5] Since 2009, Sweden has had a national HCC register reporting what the causes for HCC were ascribed to: HCV in 30%, alcohol in 25%, and HBV in 6% of the patients. 6 Diabetes and nonalcoholic liver disease have been reported since 2013, and they each accounted for close to 4% of HCC; for a large proportion of patients, no cause could be assigned.…”