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Abstract Details
Metabolic dysfunction-related liver disease as a risk factor for cancer
BMJ Open Gastroenterol. 2022 Mar;9(1):e000817. doi: 10.1136/bmjgast-2021-000817.
3Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca PLC, Cambridge, UK.
4Translational Science & Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
6Molecular and Clinical Medicine, University of Dundee, Dundee, UK, University of Dundee, Dundee, UK.
7Population Health and Genomics, University of Dundee, Dundee, UK c.n.a.palmer@dundee.ac.uk.
Abstract
Objective: The aim of this study was to investigate the association between obesity, diabetes and metabolic related liver dysfunction and the incidence of cancer.
Design: This study was conducted with health record data available from the National Health Service in Tayside and Fife. Genetics of Diabetes Audit and Research Tayside, Scotland (GoDARTS), Scottish Health Research Register (SHARE) and Tayside and Fife diabetics, three Scottish cohorts of 13 695, 62 438 and 16 312 patients, respectively, were analysed in this study. Participants in GoDARTS were a volunteer sample, with half having type 2 diabetes mellitus(T2DM). SHARE was a volunteer sample. Tayside and Fife diabetics was a population-level cohort. Metabolic dysfunction-related liver disease (MDLD) was defined using alanine transaminase measurements, and individuals with alternative causes of liver disease (alcohol abuse, viruses, etc) were excluded from the analysis.
Results: MDLD associated with increased cancer incidence with a HR of 1.31 in a Cox proportional hazards model adjusted for sex, type 2 diabetes, body mass index(BMI), and smoking status (95% CI 1.27 to 1.35, p<0.0001). This was replicated in two further cohorts, and similar associations with cancer incidence were found for Fatty Liver Index (FLI), Fibrosis-4 Index (FIB-4) and non-alcoholic steatohepatitis (NASH). Homozygous carriers of the common non-alcoholic fatty liver disease (NAFLD) risk-variant PNPLA3 rs738409 had increased risk of cancer. (HR=1.27 (1.02 to 1.58), p=3.1×10 -2). BMI was not independently associated with cancer incidence when MDLD was included as a covariate.
Conclusion: MDLD, FLI, FIB-4 and NASH associated with increased risk of cancer incidence and death. NAFLD may be a major component of the relationship between obesity and cancer incidence.