Metabolic dysfunction-associated steatotic liver disease and cancer risk: A cohort study.

Background: Fatty liver disease may be associated with increased risks of intrahepatic and extrahepatic cancers. Our objective was to investigate associations between new subcategories of steatotic liver disease (SLD) recently proposed by nomenclature consensus group and cancer risk.

Methods: A total of 283 238 participants from the UK Biobank were included. Based on information on cardiometabolic factors, alcohol consumption and the specific aetiology of SLD, individuals were categorized into four groups: no SLD (n = 170 885), metabolic dysfunction-associated steatotic liver disease (MASLD, n = 74 510), MASLD with increased alcohol intake (MetALD, n = 23 320) and other SLD (n = 6718). Outcomes were overall incident cancer (n = 39 352) and 21 site-specific cancers. The Cox proportional hazards model was used to estimate relationships between subcategories of SLD and cardiometabolic factors in MASLD with cancer risk. Population attributable risk (PAR) of cancer associated with SLD was estimated.

Results: MASLD was the most prevalent SLD in the general population. All SLD subcategories were associated with elevated risks of overall cancer, digestive system cancers (except gastric cancer) and breast cancer (HRs 1.079-4.663). Additionally, MASLD was associated with increased risks of renal cancer, endometrial cancer and Hodgkin lymphoma. Compared to MetALD and other SLDs, MASLD has a higher PAR% for the majority of aforementioned cancers. This could be largely explained by its common metabolic abnormalities, dominantly characterized by overweight/obesity and elevated blood pressure, concomitant with hyperglycaemia and hyperlipidaemia.

Conclusions: All subcategories of SLD, particularly MASLD with multiple metabolic abnormalities, were associated with increased risks of multiple cancers, providing a new perspective for cancer prevention.