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

## TL;DR

This study shows that liver disease linked to metabolic issues increases colorectal cancer risk in Korean women, especially younger and non-obese individuals.

## Contribution

The study identifies MASLD as a risk marker for colorectal cancer in metabolically healthy-appearing women.

## Key findings

- MASLD increases colorectal cancer risk in Korean women, particularly those aged 40–49 years.
- Women with MASLD and waist < 85 cm or without dyslipidemia show a higher risk of colorectal cancer.
- MASLD is associated with a 10% increased risk of colorectal cancer after adjusting for multiple factors.

## Abstract

Using a nationwide screening cohort of 483,401 Korean women, we found that metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of incident colorectal cancer. Excess risk was pronounced in women aged 40–49 years, those without dyslipidemia, and those with waist < 85 cm. These findings suggest that MASLD could serve as an important marker for risk stratification, even in individuals who may appear metabolically healthy by conventional standards, thereby helping to identify women who might benefit from closer clinical attention and metabolic management.

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.