Investigators have found that the risk of colorectal cancer may vary among steatotic liver disease subgroups and could be higher in patients with alcoholic liver disease, according to a recent study published by Kimura et al in Clinical Gastroenterology and Hepatology.
Background
Lifestyle-related conditions have become increasingly prevalent, representing a major health crisis. For instance, nonalcoholic fatty liver disease—which has been redefined under the umbrella term steatotic liver disease—has been shown to affect more than 25% of the world’s population. In addition, the disease has emerged as a heterogenous condition closely linked to metabolic dysfunction, diabetes, and obesity, constituting a risk for severe complications such as hepatocellular carcinoma and cardiovascular disease.
Although alcohol consumption and obesity are established risk factors for colorectal cancer, a leading cause of cancer-related morbidity and mortality, mounting evidence supports the association between steatotic liver disease and colorectal cancer.
Steatotic liver disease is classified based on alcohol intake into three subgroups: metabolic dysfunction–associated steatotic liver disease, metabolic dysfunction–associated steatotic liver disease with increased alcohol intake, and alcohol-associated liver disease. As a result of the emerging heterogeneity of liver diseases, colorectal cancer risk variations across different steatotic liver disease subgroups remain unknown.
Study Methods and Results
In this nationwide population-based study, the investigators compared the risk and incidence of colorectal cancer across patients with steatotic liver disease and individuals without known liver disease.
“Identifying and screening patients with [steatotic liver disease] at a higher risk of developing colorectal cancer can enable early detection and improve patient outcomes. Physicians can raise awareness among patients with [steatotic liver disease] about their increased [colorectal cancer] risk, promoting regular screening,” emphasized lead study author Takefumi Kimura, MD, PhD, of the Division of Gastroenterology in the Department of Medicine at the Shinshu University School of Medicine in Japan.
After a follow-up of 4.5 years, the investigators observed that 0.19% of patients were diagnosed with colorectal cancer. The risk of colorectal cancer was 1.73 times higher among patients with alcoholic liver disease, 1.36 times higher among those with metabolic dysfunction–associated steatotic liver disease with increased alcohol intake, and 1.28 times higher among those with metabolic dysfunction–associated steatotic liver disease.
Conclusions
The findings highlighted differences in colorectal cancer risk across different subgroups of steatotic liver disease, underscoring the need for comprehensive colorectal cancer screening and risk stratification based on the new consensus-based definitions of liver disease.
The investigators indicated that the differences in colorectal cancer risk across the different subgroups may be attributed to their underlying pathology and interactions with other comorbidities. Mechanistically, alcohol may trigger colorectal cancer development through the production of toxic metabolites, oxidative stress, and DNA damage. Conversely, metabolic dysfunction–associated steatotic liver disease is often associated with increased inflammation, metabolic dysfunction, and insulin resistance—which could elevate the risk of colorectal cancer.
“Our findings are based on data from approximately 6.38 million individuals, providing robust evidence of the individual and synergistic effects of alcohol and metabolic dysfunction on [colorectal cancer] risks. Enhanced and targeted screening programs for high-risk groups, such as [among patients with alcoholic liver disease] and [metabolic dysfunction–associated steatotic liver disease with increased alcohol intake], are crucial for early [colorectal cancer] detection and reducing [colorectal cancer]–related deaths,” Dr. Kimura concluded.
Disclosure: For full disclosures of the study authors, visit cghjournal.org.
