Uncovering the Role of Genetic Variants in COLON Cancer Risk

Recent research has shed light on the functions of previously mysterious genetic variants associated with an increased risk of colon cancer. The study, conducted by the University of Michigan and published in The American Journal of Human Genetics, focuses on mutations within the MUTYH gene, which plays a vital role in DNA repair processes. Variants in this gene are known to contribute to abnormal cell growth in the colon, elevating the risk of developing deadly colon cancer. Notably, these variants are quite common, with approximately 2% of the U.S. population carrying risk-related mutations.

The researchers employed an innovative approach by creating a comprehensive library of 10,941 MUTYH variants, allowing for detailed functional assessment. They utilized a DNA-repair reporter system that detects oxidative damage repair efficiency by fluorescence, enabling the classification of variants into functional and non-functional groups. This method successfully distinguished between benign and harmful mutations, including many missense variants that had previously been uncertain.

By comparing their findings with clinical data from the ClinVar database, the team validated the pathogenicity of numerous MUTYH mutations, including those linked to later-onset and milder forms of polyp development. This functional analysis provides crucial insights into which variants pose significant health risks, aiding in more precise genetic risk assessment.

Genetic testing currently offers limited insights for individuals with family histories of colon cancer due to the prevalence of variants of uncertain significance. The new methodology marks a significant step towards interpreting these genetic differences more accurately, empowering individuals with better information for disease prevention. Dr. Jacob Kitzman emphasized the importance of understanding how specific mutations affect gene function to enable personalized medical strategies and improved prevention efforts.

This study underscores the need for ongoing basic science research to transform genetic data into actionable health insights, potentially saving lives through early detection and preventive care.

Source: https://medicalxpress.com/news/2025-07-function-mysterious-variants-gene-linked.html