Mendelian randomization study for genetically predicted polyunsaturated fatty acids levels on overall cancer risk and mortality
Menée au Royaume-Uni à l'aide d'une méthode de randomisation mendélienne et de données portant sur 46 155 patients atteints d'un cancer et 270 342 témoins, cette étude évalue l'association entre les niveaux de 6 acides gras poly-insaturés et le risque de développer la maladie ou la mortalité
Background : Observational studies evaluating the link between polyunsaturated fatty acids (PUFAs) and cancers have yielded mixed findings. We used Mendelian randomization (MR) to evaluate whether genetic evidence supports a causal role for PUFAs on overall cancer outcomes. Materials and Methods : We identified genetic instruments for 6 PUFAs from previous literature and evaluated their association with overall cancer risk (46,155 cases, 270,342 controls) and cancer mortality (6,998 deaths, 270,342 controls) among the UK Biobank cohort. We used the inverse variance weighted model to combine SNP-estimates, and derived log (OR) estimates per SD change in each PUFA. Results : None of the 6 PUFAs showed association with overall cancer risk or mortality, with narrow CI ruling out all but very small effects e.g. AA overall cancer risk (OR = 1.02, 95% CI 1.00 - 1.03). Sex-specific analysis revealed no associations except ALA for potentially reducing cancer risk in men (OR = 0.92, 95% CI 0.86 - 0.98, P= 0.02); however, this was non-significant after multiple testing correction. From individual cancers, only colorectal cancer showed evidence for a causal association for higher AA levels (OR = 1.05, 95% CI 1.03 - 1.07), with similar results for the other correlated PUFAs. Conclusions : Our study provides no support for the hypothesis that PUFAs reduce overall cancer risk or mortality. Higher AA levels increased the risk for colorectal cancer. Impact : Our well powered MR study provides robust causal inferences for the PUFAs on overall cancer risk and mortality. Future larger studies are warranted to replicate the individual cancer findings.