Low Liver Enzyme Levels Associated with Higher Early-Onset Colorectal Cancer Risk

Epic Research released an analysis in September 2026 that examined routine laboratory results from more than 11,000 U.S. adults aged 18-44 who had undergone a colorectal-cancer screening test between 2017 and 2025. Individuals whose aspartate transaminase (AST) or alanine transaminase (ALT) levels were below 14 U/L had a markedly higher likelihood of being diagnosed with early-onset colorectal cancer (EOCRC) within a year of screening—65 % higher for low AST and 68 % higher for low ALT—compared with peers whose enzyme levels fell in the 14-29 U/L range. AST >= 30 U/L and ALT >= 30 U/L were linked to 22 % and 29 % lower likelihoods, respectively. Rising enzyme values in the three years before screening were also associated with reduced risk (27 % lower for AST, 26 % lower for ALT).

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Colorectal cancer is now the leading cause of cancer death among U.S. adults under 50, prompting the American Cancer Society in May 2026 to add a blood-based test (the Shield test) to its screening options for average-risk adults 45 and older. Colonoscopy remains the gold standard, and routine blood work has not previously been used to flag EOCRC. The Epic analysis explores whether common metabolic markers might signal undiagnosed disease in younger patients.

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• Sample: >11,000 adults, ages 18-44, with at least one AST or ALT test in the three years preceding a colorectal-cancer screening.

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• Low AST (<14 U/L): 65 % higher odds of EOCRC.

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• Low ALT (<14 U/L): 68 % higher odds of EOCRC.

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• High AST (>=30 U/L): 22 % lower odds.

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• High ALT (>=30 U/L): 29 % lower odds.

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• Rising AST over three years: 27 % lower odds.

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• Rising ALT over three years: 26 % lower odds.

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• No significant association for triglycerides, cholesterol, potassium, or for decreasing enzyme levels.

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• A UK cohort of 375,000 participants (2006-2010) reported a similar inverse relationship between AST/ALT levels and long-term colorectal-cancer risk.

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Kersten Bartelt, clinician and researcher at Epic Research, emphasized that the analysis identifies an association, not causation, and that low enzyme levels may reflect reduced muscle mass or nutritional status. Dr. Marc Fenster, gastroenterologist at Episcopal Health Services, noted that the findings add a “signal” to the broader search for EOCRC risk markers but do not warrant changes to current screening protocols. Dr. Daniel Sussman of the University of Miami highlighted the need for careful validation, stressing that the low-enzyme values fall within typical reference ranges. Mingyang Song, associate professor at Harvard T.H. Chan School of Public Health, suggested that lower enzyme activity might indicate diminished metabolic capacity, potentially increasing susceptibility to carcinogens, yet warned against clinical recommendations based solely on these labs. Caleb Cox, head of research at Epic, framed the work as exploratory, stating that further investigation is required to determine whether low AST/ALT levels can help identify underlying drivers of the EOCRC rise.

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