JIMKI Jurnal Ilmiah Mahasiswa Kedokteran Indonesia · Jan 13, 2026
Risk Factors for Colorectal Cancer Based on Genetic Assessment: A Literature Review of Mendelian Randomization Studies
By Muabbad T, Qurais N, Fakhihah A et al.
INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death worldwide. Although various risk factors have been identified, the causal relationships between these factors and CRC incidence are still not fully understood because of potential bias, confounding, and reverse causality in observational studies. Mendelian Randomization (MR) analysis offers an alternative approach using genetic variation as an instrument to test causal relationships. METHODS: This literature review used a narrative review method to examine MR studies published in the last 10 years that evaluated the relationships between genetically predicted risk factors and CRC incidence. The literature was obtained through systematic searches of the PubMed and Cochrane databases, with selection based on topic relevance, full-text availability, and publication quality. DISCUSSION: Seven MR studies were analyzed. The results showed causal relationships between increased total bilirubin levels, acceleration of the GrimAge epigenetic clock, increased insulin-like growth factor-1 (IGF-1) levels, alcohol consumption, exposure to air pollutants (PM2.5), and the presence of certain gut microbiota (Porphyromonadaceae, Anaerotruncus, Intestinibacter) and increased CRC risk. Conversely, Gammaproteobacteria and Enterobacteriaceae showed protective effects. This study has limitations, including horizontal pleiotropy and limitations of the sample populations, which were mostly from Europe and East Asia. CONCLUSIONS: Several genetically predicted exposures have been shown to have causal relationships with CRC incidence. Further research based on Southeast Asian populations, particularly Indonesia, is needed to confirm these findings in different genetic and environmental contexts.