Young adults with metabolic dysfunction-associated steatotic liver disease have an increased risk of early-onset cancer.

Objective: 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 aged 20-39 years between 2013 and 2014 were included and followed up until December 31, 2022. Individuals were categorized into non-SLD, metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) groups. Hepatic steatosis was defined as a fatty liver index ≥60. The primary outcome was all-cancer, 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% CI, 1.16-1.22; P<0.001) MetALD (HR, 1.12; 95% CI, 1.07-1.18; P<0.001), and ALD (HR, 1.21; 95% CI, 1.12-1.31; P<0.001) groups had a higher risk of all cancers compared to 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.