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

About this Publication
Title
Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.
Pubmed ID
32967863 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Epidemiol Biomarkers Prev. 2020 Dec; Volume 29 (Issue 12): Pages 2735-2739
Authors
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, ...show more 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
Affiliations
  • Division of Cancer Epidemiology, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Division of General Internal Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee.
  • Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England, United Kingdom.
  • Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida.
  • Departments of Obstetrics and Gynecology, Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
...show more
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Lunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada.
  • Division of Cancer Epidemiology, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • International Agency for Research on Cancer, Lyon, France.
  • Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • 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.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
  • Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
  • Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Yale Cancer Center, New Haven, Connecticut.
  • Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
  • Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
  • Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • Epidemiology and Genomics Research Program, Division of Cancer Control and Population Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center, Madrid, Spain.
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain.
  • CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, Texas.
  • Department of Epidemiology and Environmental Health, University of Buffalo, Buffalo, New York.
  • Departments of Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, New York.
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
  • Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
  • Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
  • Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
  • 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.
  • 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.
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.

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