Colorectal cancer (CRC) is one of the most common cancers worldwide, necessitating the identification of risk factors and preventive measures. Fatty acids, vital nutrients involved in various bodily functions, have been linked to CRC
however, findings are inconsistent. This Mendelian randomization study utilized data from the UK Biobank and included 18 fatty acid-related phenotypes. We used single-nucleotide polymorphisms as instrumental variables to examine the Causal connections between fatty acids and CRC. Statistical analysis involved the inverse-variance-weighted, Mendelian randomization-Egger, and weighted median methods to ensure robust findings. Our analysis revealed that docosahexaenoic acid and omega-3 fatty acids were positively associated with CRC risk. No significant associations were found between CRC and total fatty acids, saturated fatty acids, polyunsaturated fatty acids, or monounsaturated fatty acids. The degree of unsaturation was positively associated with CRC, while the ratio of omega-6 to omega-3 fatty acids was negatively associated. The study highlights a positive association between docosahexaenoic acid, omega-3 fatty acids, and CRC, suggesting that specific fatty acids may influence CRC risk. Further research in diverse populations is needed to confirm these findings and explore the underlying mechanisms.