Young Adults With Metabolic Dysfunction–Associated Steatotic Liver Disease Have an Increased Risk of Early-Onset Cancer: A Nationwide Cohort Study Differentiating the Risk of 23 Site-Specific Cancers

Background & Aims We investigated the association between subtypes of steatotic liver disease (SLD) and 23 site-specific cancers in a nationwide cohort of young Korean adults. Methods From a nationwide health screening database in Korea, 2,877,245 young adults 20–39 years of age between 2013 and 2014 were included and followed up until December 31, 2022. Individuals were categorized into non-SLD, metabolic dysfunction–associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) groups. Hepatic steatosis was defined as a fatty liver index ≥30. The primary outcome was all cancers, while secondary outcomes included 23 site-specific cancers. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). Results During 22,819,681 person-years of follow-up, 46,729 incident cancer cases developed. The MASLD (HR, 1.19; 95% confidence interval [CI], 1.16–1.22; P < .001) MetALD (HR, 1.12; 95% CI, 1.07–1.18; P < .001), and ALD (HR, 1.21; 95% CI, 1.12–1.31; P < .001) groups had a higher risk of all cancers compared with the non-SLD group. Most obesity-related cancers showed increased risk in individuals with either MASLD or MetALD. There was an increasing trend in all-cancer risk with increasing number of cardiometabolic risk factors among MASLD. Alcohol consumption had a modest effect on overall cancer risk, with varying effects on specific cancer types. Conclusions Young adults with MASLD, MetALD, or ALD are at increased risk of developing early-onset cancer.