Mendelian randomization analysis of n-6 polyunsaturated fatty acid levels and pancreatic cancer risk
Menée à l'aide d'une méthode de randomisation mendélienne et de données d'études d'association sur le génome entier portant sur 9 269 patients atteints d'un cancer du pancréas et sur 12 530 témoins, cette étude analyse l'association entre les taux plasmatiques (estimés à partir de données génétiques) d'acides gras polyinsaturés à longue chaîne n-6 et le risque de développer la maladie
Background: Whether circulating polyunsaturated fatty acids (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk (estimates per one standard deviation increase in each PUFA-specific weighted genetic score using summary statistics: Linoleic acid - odds ratio (OR) = 1.00, 95% confidence interval (CI) 0.98-1.02; arachidonic acid - OR = 1.00, 95% CI 0.99-1.01; dihomo-gamma-linolenic acid - OR = 0.95, 95% CI 0.87-1.02). The OR estimates remained virtually unchanged after adjustment for covariates, using of individual level data or summary statistics, or stratification by age and sex. Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.