Abstract

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.

Authors	Ghoneim, Dalia H; Zhu, Jingjing; Zheng, Wei; Long, Jirong; Murff, Harvey J; Ye, Fei; Setiawan, Veronica Wendy; Wilkens, Lynne R; Khankari, Nikhil K; Haycock, Philip; Antwi, Samuel O; Yang, Yaohua; Arslan, Alan A; Beane Freeman, Laura E; Bracci, Paige M; Canzian, Federico; Du, Mengmeng; Gallinger, Steven; Giles, Graham G; Goodman, Phyllis J; Kooperberg, Charles; Le Marchand, Loic; Neale, Rachel E; Scelo, Ghislaine; Visvanathan, Kala; White, Emily; Albanes, Demetrius; Amiano, Pilar; Andreotti, Gabriella; Babic, Ana; Bamlet, William R; Berndt, Sonja I; Brais, Lauren K; Brennan, Paul; Bueno-de-Mesquita, Bas; Buring, Julie E; Campbell, Peter T; Rabe, Kari G; Chanock, Stephen J; Duggal, Priya; Fuchs, Charles S; Gaziano, J Michael; Goggins, Michael G; Hackert, Thilo; Hassan, Manal M; Helzlsouer, Kathy J; Holly, Elizabeth A; Hoover, Robert N; Katzke, Verena; Kurtz, Robert C; Lee, I-Min; Malats, Nuria; Milne, Roger L; Murphy, Neil; Oberg, Ann L; Porta, Miquel; Rothman, Nathaniel; Sesso, Howard D; Silverman, Debra T; Thompson, Ian M; Wactawski-Wende, Jean; Wang, Xiaoliang; Wentzensen, Nicolas; Yu, Herbert; Zeleniuch-Jacqotte, Anne; Yu, Kai; Wolpin, Brian M; Jacobs, Eric J; Duell, Eric J; Risch, Harvey A; Petersen, Gloria M; Amundadottir, Laufey T; Kraft, Peter; Klein, Alison P; Stolzenberg-Solomon, Rachel Z; Shu, Xiao-Ou; Wu, Lang
Journal	Cancer Epidemiology Biomarkers and Prevention
Pages	2735-2739
Volume	29
Date	1/09/2020
Grant ID	HHSN268201600002C
Funding Body	NHLBI NIH HHS
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1158/1055-9965.EPI-20-0651