Work

Estimation of controlled direct effects of polyunsaturated fatty acids on colorectal adenoma risk using inverse probability weighting

Year: 2026

Type: article

Abstract: Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) exert putatively divergent effects on inflammation, partly through differential production of prostaglandin E2 (PGE2), a pro-inflammatory metabolite implicated in colorectal carcinogenesis. To elucidate PUFA effects independent of downstream PGE2, we estimated the controlled direct effect (CDE) of 5 PUFAs on colorectal adenoma risk while holding the major urinary metabolite of PGE2 (or PGE-M) levels constant. We analyzed data from 819 participants in the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case-control study conducted in Nashville, Tennessee between 2003 and 2010. The analytic sample included participants with measurements of red blood cell PUFAs, PGE-M concentration, and relevant covariates. Total effects were estimated using multivariable regression, and CDEs were estimated using inverse probability weighting. Our analysis suggested a notable 34% reduction (ORCDE = 0.66, 95% CI = 0.54, 0.82) in colorectal adenoma risk for the CDE of 1 SD increase in omega-3 eicosapentaenoic acid (EPA) levels, independent of PGE-M levels. Our findings suggest a putative effect of EPA in reducing colorectal adenomas independent of changes in downstream PGE-M levels in the TCPS population, highlighting its potential role in colorectal adenoma prevention.

Source: AJE Advances Research in Epidemiology

DOI: 10.1093/ajeadv/uuag034