Abstract
BACKGROUND AND AIMS: Gastrointestinal(GI) cancer poses a significant threat to human health and safety, with studies suggesting a potential correlation between fatty acids(FAs) and GI diseases. We aim to comprehensively explore the association between plasma FAs and the risk of GI cancer and assess the causal effect of FAs on GI cancer risk through Mendelian randomization (MR). METHODS: This prospective cohort study includes 230,415 cancer-free participants from the UK Biobank. We utilized Cox regression, restricted cubic splines, and accelerated failure time models to analyze the correlation between 17 circulating FAs and the risk of the overall GI cancer and five site-specific GI cancers, including esophageal cancer, stomach cancer, colorectal cancer, liver cancer and pancreatic cancer. And two-sample MR was employed to explore causal effects. RESULTS: Over an average follow-up of 12.0 years, a total of 4,682 GI cancer cases were recorded. 14 FAs were found to be associated with GI cancer risk, with eleven exhibiting inhibitory effects, particularly significant in esophageal and liver cancers. MR results indicated causal associations between DHA/FA, SFA/FA, LA/FA, PUFA, and GI cancer risk. CONCLUSION: Circulating FAs are closely associated with GI cancer risk, aiding in the screening of high-risk populations. Moreover, targeted control of FAs levels may help reduce the risk of GI cancer occurrence in populations.