Exploring the Syndemic of Steatotic Liver Disease, Socioeconomic Inequities and Cancer Risk in the UK Biobank

Background: Steatotic liver disease (SLD), formerly known as fatty liver disease, is associated with increased cancer risk. However, the impact of socioeconomic inequities remains understudied. This study investigates the relationship between SLD, socioeconomic position (SEP) and cancer risk using a syndemic framework. Methods: Using UK Biobank data, we defined metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD) and alcoholic liver disease (ALD), based on the Fatty Liver Index, cardiometabolic criteria and alcohol consumption. SEP was derived via latent class analysis using education, household income and employment. We used Cox proportional hazards models to examine the associations between MASLD, MetALD and ALD and the incidence of any, obesity-related and digestive cancers. We then evaluated the combined effect of these SLD subcategories and SEP on cancer outcomes. Results: Among 325 476 individuals, 91 651 had MASLD, 25 649 MetALD and 8005 ALD. Over 11.7 years median follow-up, 35 775 first incident cancers occurred (15 426 obesity-related; 6959 digestive). MASLD, MetALD and ALD were each associated with an increased risk of all cancer outcomes (hazard ratios [HR] ranging from 1.09 to 1.73). The combination of MASLD and low SEP was associated with an increased risk of any (HR: 1.14, 95% CI: 1.08–1.19), obesity-related (HR: 1.25, 95% CI: 1.16–1.33) and digestive cancers (HR: 1.37, 95% CI: 1.23–1.53). Similar trends were observed for individuals with MetALD or ALD and low SEP across all cancer outcomes. Conclusion: SLD is independently associated with increased risk of any, obesity-related and digestive cancers. These risks are amplified by socioeconomic inequities, highlighting the need for integrated approaches that consider both clinical and social determinants of health.