Causal Relationships between Polyunsaturated Fatty Acids and Colon Polyps: A Two-Sample Mendelian Randomization Study.

Abstract

Epidemiological studies have shown that fatty acids, especially polyunsaturated fatty acids (PUFAs), influence colorectal carcinogenesis. Colon polyps, particularly those identified as precancerous, are a frequently encountered phenomenon associated with PUFAs. However, the results are inconsistent. Therefore, we investigated the effect of PUFAs on colon polyps in individuals of European ancestry. Single nucleotide polymorphisms correlating with PUFAs and colon polyps were derived from extensive genome-wide association studies, encompassing a discovery cohort of 135,006 samples and a corresponding validation set with 114,999 samples. Causality was assessed by employing a range of techniques, such as inverse variance weighted (IVW), weighted median, MR-Egger, and simple and weighted modes. The analysis was complemented with sensitivity checks using leave-one-out and heterogeneity evaluation through MR-IVW and Cochran's Q. A thorough analysis was performed to examine the causal effects of PUFAs on the development of colon polyps. The findings indicated that levels of Omega-3 fatty acids (OR = 1.0014, 95% CI 1.0004-1.0024, p = 0.004), the ratio of Docosahexaenoic acid (DHA)/total fatty acids (FAs) (DHA/totalFA; OR = 1.0015, 95% CI 1.0002-1.0028, p = 0.023), and the ratio of Omega-3/totalFA (Omega-3/totalFA; OR = 1.0013, 95% CI 1.0003-1.0022, p = 0.010) were identified as biomarkers associated with an increased risk of colon polyps. Conversely, the ratio of Omega-6/Omega-3 (OR = 0.9986, 95% CI 0.9976-0.9995, p = 0.003) and the ratio of Linoleic acid (LA)/totalFA (LA/totalFA; OR = 0.9981, 95% CI 0.9962-0.9999, p = 0.044) were negatively associated with susceptibility to colon polyps. The MR-Egger and MR-IVW analysis revealed that pleiotropy and heterogeneity did not significantly impact the outcomes. This study has uncovered a possible adverse effect of PUFAs, notably Omega-3, on the formation of colon polyps. Elevated Omega-3 levels were correlated with a heightened risk of colon polyps.