Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

Abstract

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.

• Authors: 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 Goodman, Charles Kooperberg, Loïc Le Marchand, Rachel E Neale, Ghislaine Scelo, Kala Visvanathan, Emily White, Demetrius Albanes, Pilar Amiano, Gabriella Andreotti, 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, Núria Malats, Roger L Milne, Neil Murphy, Ann L Oberg, Miquel Porta, Nathaniel Rothman, Howard D Sesso, Debra T Silverman, Ian M Thompson Jr, 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
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 29 Issue 12 Pg. 2735-2739 (12 2020) ISSN: 1538-7755 [Electronic] United States
• PMID: 32967863 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Fatty Acids, Omega-6

Topics

• Aged
• Fatty Acids, Omega-6 (blood)
• Female
• Humans
• Male
• Mendelian Randomization Analysis (methods)
• Middle Aged
• Pancreatic Neoplasms (genetics, pathology)
• Risk Factors