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

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 PGE2, are key for polyp formation during early-stage colorectal carcinogenesis