Association Between Nonalcoholic Fatty Liver Disease and Risk of Early-onset Colorectal Cancer

Abstract

Background & aims: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of colorectal cancer (CRC) but has rarely been investigated in adults aged <50 years. We assessed the relationship between NAFLD and early-onset CRC according to anatomical site.

Methods: This population-based cohort study included adults aged 20 to 49 years who underwent health checkups in 2009 under the Korean National Health Insurance Service with follow-up until 2019. NAFLD was defined as a fatty liver index (FLI) of ≥60. Early-onset CRC diagnosed during follow-up was confirmed using claims data.

Results: A total of 4,657,825 subjects were categorized into NAFLD (FLI ≥60), borderline NAFLD (30 ≤FLI <60), and no NAFLD (FLI <30) groups, with 2733 cases of early-onset CRC identified during a median follow-up of 9.3 years. Early-onset CRC risk was significantly higher in the NAFLD (adjusted hazard ratio, 1.24; 95% confidence interval, 1.17-1.31) and borderline NAFLD (adjusted hazard ratio, 1.12; 95% confidence interval, 1.07-1.17) groups compared with the no-NAFLD group. A dose-response association between FLI and early-onset CRC risk was observed only in the left colon and rectum. Subgroup analysis revealed stronger associations in males, individuals aged 20 to 29 years, and non-diabetic participants (P for interaction < .05).

Conclusions: NAFLD is associated with an increased risk of early-onset CRC, particularly in the left colon and rectum. These findings highlight the need for multifaceted preventive strategies, including lifestyle interventions and expanded screening for younger populations with NAFLD.

Keywords: Colorectal Cancer; Early-onset Colorectal Cancer; Nonalcoholic Fatty Liver Disease.