Objective  To evaluate the causal relationship between polyunsaturated fatty acids (PUFA) and colorectal cancer (CRC) through a two-sample Mendelian randomization (MR) study.

Methods  Based on genome-wide association study (GWAS) data, genetic variations related to PUFA were used as instrumental variables, and CRC was extracted from the GWAS dataset as the outcome indicator. The inverse-variance weighted method MR-Egger regression and weighted median method were used as the main analytical method to assess the causal relationship between omega-3 fatty acids, omega-6 fatty acids, the ratio of omega-3 to total fatty acids, the ratio of omega-6 to total fatty acids, and the omega-6 to omega-3 ratio with CRC risk.

Results  The inverse variance weighting analysis showed that omega-3 fatty acids [OR=1.14, 95%CI(1.06, 1.23), P=0.014], omega-6 fatty acids [OR=1.10, 95%CI(1.03, 1.18), P=0.007], and the omega-6 to omega-3 ratio [OR=0.91, 95%CI(0.84, 0.99), P=0.006] have direct causal relationships with CRC. The ratio of omega-3 to total fatty acids [OR=1.09, 95%CI(0.94, 1.26), P=0.164] and the ratio of omega-6 to total fatty acids [OR=1.07, 95%CI(0.97, 1.18), P=0.226] have no causal relationship with CRC.

Conclusion  The MR analysis results suggest that there are causal relationships between omega-3 fatty acids, omega-6 fatty acids, and the omega-6 to omega-3 ratio with CRC, while there is no causal relationship for the ratio of omega-3 to total fatty acids and the ratio of omega-6 to total fatty acids.

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