Heterogeneous Colorectal Cancer Risk in Women with Metabolic Dysfunction-Associated Steatotic Liver Disease by Age, Lipid, and Waist-Circumference: A Nationwide Cohort Study

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly common and linked to obesity; however, its association with colorectal cancer (CRC) risk in women remains unclear. Materials and Methods: This retrospective cohort study used the Korean National Health Insurance Service health-screening database, including 483,401 women aged 40-59 years examined between 2013 and 2016, followed through 2021. MASLD was defined as hepatic steatosis (hepatic steatosis index >= 36 or ICD-10 K76.0) with >= 1 metabolic abnormality and no heavy alcohol use (>= 20 g/day). Incident CRC (ICD-10 C18-C20) was analyzed using Cox regression adjusted for demographic, socioeconomic, and metabolic variables. Effect modification was tested across key covariates. Results: MASLD was found in 128,642 participants (26.6%). During a median 7.5-year follow-up, 2432 CRC cases occurred (702 with MASLD). The 7-year cumulative CRC risk was higher in the MASLD group (0.47% vs. 0.43%; p = 0.006). MASLD independently increased CRC risk (adjusted HR 1.10; 95% CI 1.00-1.20). Effect modification was observed for age, dyslipidemia, and waist circumference. MASLD significantly increased CRC risk among women aged 40-49 years (HR 1.26; 95% CI 1.05-1.49), those without dyslipidemia (HR 1.15; 95% CI 1.03-1.28), and with waist < 85 cm (HR 1.15; 95% CI 1.02-1.30). Conclusions: MASLD modestly increases CRC risk in Korean women, particularly among younger, normolipidemic, and non-obese individuals, indicating the need for age- and metabolism-specific risk stratification and suggesting a need for closer clinical attention and metabolic optimization.