Population-Attributable Fractions of Personal Comorbidities for Liver, Gallbladder, and Bile Duct Cancers

Abstract

Background: We aim to estimate population-attributable fractions (PAF) for 13 comorbidities potentially predisposing to hepatobiliary cancer of hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cancers of the intrahepatic and extrahepatic bile ducts (ICC and ECC), and ampullary cancer. Methods: Patients were identified from the Swedish Inpatient Register from 1987 to 2018 and cancers from the Swedish Cancer Registry from 1997 through 2018. PAFs were calculated for each comorbidity-associated cancer using a cohort study design. Results: For male HCC, the major individual comorbidities (PAF > 10) were diabetes, alcohol-related liver disease, and hepatitis C virus infection. For female HCC, diabetes and autoimmune diseases were important contributors. For female GBC, gallstone disease was an overwhelming contributor, with a PAF of 30.57%, which was also important for men. The overall PAF for male ICC was almost two times higher than the female one. For ECC and ampullary cancer, infection of bile ducts was associated with the highest PAF. Conclusions: The 13 comorbidities accounted for 50% or more of the potential etiological pathways of each hepatobiliary cancer except female ICC. The underlying convergent mechanism for these cancers may be chronic inflammation lasting for decades and thus offering possibilities for intervention and disease monitoring.

Integrated Pleiotropic Gene Set Unveils Comorbidity Insights across Digestive Cancers and Other Diseases

“…For instance, various gastrointestinal complications, including increased odds ratio or relative risk of esophageal cancer, stomach cancer, liver diseases (including hepatobiliary cancer) and pancreatic cancer, have been associated with obesity [5]. In the case of male hepatocellular carcinoma, diabetes, alcohol-related liver disease and hepatitis C virus infection were identified as major individual comorbidities, with population-attributable fractions exceeding 10% [6]. In China, cardiometabolic diseases, particularly hypertension, were the most common comorbidities of gastric cancer and esophageal cancer, with hypertension being predominant.…”