Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.
Ghoneim DH, Zhu J, Zheng W, Long J, Murff HJ, Ye F, Setiawan VW, Wilkens LR, Khankari NK, Haycock P, Antwi SO, Yang Y, Arslan AA, Beane Freeman LE, Bracci PM, Canzian F, Du M, Gallinger S, Giles GG, Goodman PJ, Kooperberg C, Le Marchand L, Neale RE, Scelo G, Visvanathan K, White E, Albanes D, Amiano P, Andreotti G, Babic A, Bamlet WR, Berndt SI, Brais LK, Brennan P, Bueno-de-Mesquita B, Buring JE, Campbell PT, Rabe KG, Chanock SJ, Duggal P, Fuchs CS, Gaziano JM, Goggins MG, Hackert T, Hassan MM, Helzlsouer KJ, Holly EA, Hoover RN, Katske V, Kurtz RC, Lee IM, Malats N, Milne RL, Murphy N, Oberg AL, Porta M, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Yu H, Zeleniuch-Jacquotte A, Yu K, Wolpin BM, Jacobs EJ, Duell EJ, Risch HA, Petersen GM, Amundadottir LT, Kraft P, Klein AP, Stolzenberg-Solomon RZ, Shu XO, Wu L
BACKGROUND: Whether circulating polyunsaturated fatty acid (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 SD 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; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using 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.
- 2006-0306: Whole Genome Scan of Incident Pancreatic Cancer in the Cohort Consortium (PanScan) (Rachael Stolzenberg-Solomon - 2006)