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

Ghoneim DH 1 , Zhu J 1 , Zheng W 2 , Long J 2 , Murff HJ 3 , Ye F 4 Show all authors , Setiawan VW 5 , Wilkens LR 1 , Khankari NK 2 , Haycock P 6 , Antwi SO 7 , Yang Y 2 , Arslan AA 8 , Beane Freeman LE 9 , Bracci PM 10 , Canzian F 11 , Du M 12 , Gallinger S 13 , Giles GG 14 , Goodman PJ 15 , Kooperberg C 16 , Le Marchand L 1 , Neale RE 17 , Scelo G 18 , Visvanathan K 19 , White E 20 , Albanes D 9 , Amiano P 21 , Andreotti G 9 , Babic A 22 , Bamlet WR 23 , Berndt SI 9 , Brais LK 22 , Brennan P 18 , Bueno-de-Mesquita B 24 , Buring JE 25 , Campbell PT 26 , Rabe KG 23 , Chanock SJ 9 , Duggal P 19 , Fuchs CS 27 , Gaziano JM 28 , Goggins MG 29 , Hackert T 30 , Hassan MM 31 , Helzlsouer KJ 32 , Holly EA 10 , Hoover RN 9 , Katske V 33 , Kurtz RC 34 , Lee IM 25 , Malats N 35 , Milne RL 14 , Murphy N 36 , Oberg AL 23 , Porta M 37 , Rothman N 9 , Sesso HD 25 , Silverman DT 9 , Thompson IM 38 , Wactawski-Wende J 39 , Wang X 20 , Wentzensen N 9 , Yu H 1 , Zeleniuch-Jacquotte A 40 , Yu K 9 , Wolpin BM 22 , Jacobs EJ 41 , Duell EJ 42 , Risch HA 43 , Petersen GM 23 , Amundadottir LT 44 , Kraft P 45 , Klein AP 19 , Stolzenberg-Solomon RZ 9 , Shu XO 46 , Wu L 47

Affiliations 

  • 1 Division of Cancer Epidemiology, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii
  • 2 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
  • 3 Division of General Internal Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee
  • 4 Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
  • 5 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
  • 6 MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England, United Kingdom
  • 7 Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida
  • 8 Departments of Obstetrics and Gynecology, Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York
  • 9 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 10 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California
  • 11 Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 12 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
  • 13 Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada
  • 14 Division of Cancer Epidemiology, Cancer Council Victoria, Melbourne, Victoria, Australia
  • 15 SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 16 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 17 Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  • 18 International Agency for Research on Cancer, Lyon, France
  • 19 Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
  • 20 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 21 Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian; CIBER Epidemiología y Salud Pública, Madrid, Spain
  • 22 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 23 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota
  • 24 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
  • 25 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 26 Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
  • 27 Yale Cancer Center, New Haven, Connecticut
  • 28 Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  • 29 Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland
  • 30 Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
  • 31 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
  • 32 Epidemiology and Genomics Research Program, Division of Cancer Control and Population Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 33 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 34 Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York
  • 35 Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain
  • 36 Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
  • 37 Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
  • 38 CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, Texas
  • 39 Department of Epidemiology and Environmental Health, University of Buffalo, Buffalo, New York
  • 40 Departments of Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York
  • 41 Epidemiology Research Program, American Cancer Society, Atlanta, Georgia
  • 42 Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain
  • 43 Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut
  • 44 Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 45 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  • 46 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. lwu@cc.hawaii.edu xiao-ou.shu@vanderbilt.edu
  • 47 Division of Cancer Epidemiology, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii. lwu@cc.hawaii.edu xiao-ou.shu@vanderbilt.edu
Cancer Epidemiol Biomarkers Prev, 2020 Dec;29(12):2735-2739.
PMID: 32967863 DOI: 10.1158/1055-9965.EPI-20-0651

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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