Mendelian randomization analysis of n-6 polyunsaturated fatty acid levels and pancreatic cancer risk

Dalia H. Ghoneim, Jingjing Zhu, Wei Zheng, Jirong Long, Harvey J. Murff, Fei Ye, Veronica Wendy Setiawan, Lynne R. Wilkens, Nikhil K. Khankari, Philip Haycock, Samuel O. Antwi, Yaohua Yang, Alan A. Arslan, Laura E.Beane Freeman, Paige M. Bracci, Federico Canzian, Mengmeng Du, Steven Gallinger, Graham G. Giles, Phyllis J. GoodmanCharles Kooperberg, Loïc Le Marchand, Rachel E. Neale, Ghislaine Scelo, Kala Visvanathan, Emily White, Demetrius Albane, Pilar Amiano, Gabriella Andreott, Ana Babic, William R. Bamlet, Sonja I. Berndt, Lauren K. Brais, Paul Brennan, Bas Bueno-De-Mesquita, Julie E. Buring, Peter T. Campbell, Kari G. Rabe, Stephen J. Chanock, Priya Duggal, Charles S. Fuchs, J. Michael Gaziano, Michael G. Goggins, Thilo Hackert, Manal M. Hassan, Kathy J. Helzlsouer, Elizabeth A. Holly, Robert N. Hoover, Verena Katske, Robert C. Kurtz, I. Min Lee, Nuria Malats, Roger L. Milne, Neil Murphy, Ann L. Oberg, Miquel Porta, Nathaniel Rothman, Howard D. Sesso, Debra T. Silverman, Thompson Ian, Jean Wactawski-Wende, Xiaoliang Wang, Nicolas Wentzensen, Herbert Yu, Anne Zeleniuch-Jacquotte, Kai Yu, Brian M. Wolpin, Eric J. Jacobs, Eric J. Duell, Harvey A. Risch, Gloria M. Petersen, Laufey T. Amundadottir, Peter Kraft, Alison P. Klein, Rachel Z. Stolzenberg-Solomon, Xiao Ou Shu, Lang Wu

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)2735-2739
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Issue number12
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Medicine(all)


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