Investigation of the association between high arachidonic acid synthesis and colorectal polyp incidence: a Mendelian randomisation approach

ABSTRACT Background & Aims Arachidonic acid (ARA) is causally associated with colorectal cancer (CRC), a major public health concern. However, it is uncertain if ARA contributes to the development of colorectal polyps which are pre-malignant precursors of CRC. Therefore, this study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence using Mendelian randomisation. Methods Summary: level GWAS data from European, Singaporean, and Chinese cohorts (n=10,171) identified 4 single nucleotide polymorphisms (SNPs) associated with blood ARA levels (p< 5 × 10 −8 ). After pruning, 1 SNP was retained (rs174547; p=3.0×10 −971 ) for 2-stage Mendelian randomisation to infer the causal effect of ARA on self-reported colorectal polyp outcomes within the UK Biobank (1,391 cases; 462,933 total). Results No association between ARA and colorectal polyp incidence was observed [OR= 1.00 (95% CI: 0.99, 1.00); P-value = 0.50). Conclusions Blood levels of ARA do not associate with colorectal polyp incidence. This work supports the contention that downstream lipid mediators, such as PGE 2 , are key for polyp formation during early-stage colorectal carcinogenesis