Investigation of the association between high arachidonic acid synthesis and colorectal polyp incidence within a generally healthy UK population: a Mendelian randomisation approach

Background: Arachidonic acid (ARA) is 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. Objective: The study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence. 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 randomization. Results: No association between ARA and colorectal polyp incidence was observed (OR = 1.00; 95% CI: 0.99, 1.00; p value = 0.50) within the UK Biobank (1,391 cases; 462,933 total). Conclusions: Blood levels of ARA do not associate with colorectal polyp incidence in a general healthy population. Although not providing direct evidence, this work supports the contention that downstream lipid mediators, such as PGE2 rather than ARA itself, are key for polyp formation during early-stage colorectal carcinogenesis.