Increased Risk of Young-Onset Digestive Tract Cancers Among Young Adults Age 20-39 Years With Nonalcoholic Fatty Liver Disease: A Nationwide Cohort Study

PURPOSE Although the incidence of young-onset digestive tract cancers is increasing worldwide, their risk factors remain largely unknown. We investigated the association between nonalcoholic fatty liver disease (NAFLD) and young-onset digestive tract cancers. PATIENTS AND METHODS This nationwide cohort study included 5,265,590 individuals age 20-39 years who underwent national health screening under the Korean National Health Insurance Service between 2009 and 2012. The fatty liver index was used as a diagnostic biomarker for NAFLD. The participants were followed up until December 2018 to determine the incidence of young-onset digestive tract cancers (ie, esophageal, stomach, colorectal, liver, pancreatic, biliary tract, and gallbladder). Multivariable Cox proportional hazards models were conducted to estimate the risk after adjusting for potential confounders. RESULTS During the 38.8 million person-years of follow-up, 14,565 patients were newly diagnosed with young-onset digestive tract cancers. The cumulative incidence probability of each cancer type was consistently higher in individuals with NAFLD than in those without NAFLD (all log-rank P < .05). NAFLD was associated with an increased risk of overall digestive tract (adjusted hazard ratio [aHR], 1.16; 95% CI, 1.10 to 1.22), stomach (aHR, 1.14; 95% CI, 1.06 to 1.24), colorectal (aHR, 1.14; 95% CI, 1.06 to 1.22), liver (aHR, 1.13; 95% CI, 1.12 to 1.52), pancreatic (aHR, 1.23; 95% CI, 1.09 to 1.40), biliary tract (aHR, 1.29; 95% CI, 1.00 to 1.66), and gallbladder (aHR, 1.53; 95% CI, 1.01 to 2.31) cancer. These associations remained significant regardless of age, sex, smoking status, alcohol consumption, and obesity status (all P < .05; P for interaction >.05). The aHR for esophageal cancer was 1.67 (95% CI, 0.92 to 3.03). CONCLUSION NAFLD may be an independent, modifiable risk factor for young-onset digestive tract cancers. Our findings suggest a crucial opportunity to reduce premature morbidity and mortality associated with young-onset digestive tract cancers in the next generation.