Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization

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King, Sontoria D.Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, FL, Jacksonville, Puerto Rico (author)

Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization

Article/chapterEnglish2023

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American Association For Cancer Research (AACR),2023
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LIBRIS-ID:oai:DiVA.org:umu-214290
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-214290URI
https://doi.org/10.1158/1055-9965.EPI-23-0453DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer.METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes.RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample.CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk.IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.

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Veliginti, SwathiDivision of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, FL, Jacksonville, Puerto Rico (author)
Brouwers, Martijn C G JDivision of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands (author)
Ren, ZhewenDivision of Endocrinology and Metabolic Diseases, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands (author)
Zheng, WeiDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Setiawan, Veronica W.Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (author)
Wilkens, Lynne R.Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, HI, Honolulu, United States (author)
Shu, Xiao-OuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN, Nashville, United States (author)
Arslan, Alan A.Departments of Obstetrics and Gynecology, Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, NY, United States (author)
Beane Freeman, Laura E.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Bracci, Paige M.Department of Epidemiology and Biostatistics, University of California, CA, San Francisco, United States (author)
Canzian, FedericoGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany (author)
Du, MengmengDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, United States (author)
Gallinger, Steven J.Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, ON, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, ON, Toronto, Canada (author)
Giles, Graham G.Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, VIC, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, VIC, Melbourne, Australia (author)
Goodman, Phyllis J.SWOG Statistical Center, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Haiman, Christopher A.Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (author)
Kogevinas, ManolisCentre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain (author)
Kooperberg, CharlesDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
LeMarchand, LoicCancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, HI, Honolulu, United States (author)
Neale, Rachel E.Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia (author)
Visvanathan, KalaDepartment of Epidemiology, Johns Hopkins School of Public Health, MD, Baltimore, Liberia; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, MD, Baltimore, Liberia (author)
White, EmilyCancer Prevention Program, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Albanes, DemetriusDivision of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Andreotti, GabriellaDivision of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Babic, AnaDepartment of Medical Oncology, Dana-Farber Cancer Institute, MA, Boston, United States (author)
Berndt, Sonja I.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Brais, Lauren K.Department of Medical Oncology, Dana-Farber Cancer Institute, MA, Boston, United States (author)
Brennan, PaulGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France (author)
Buring, Julie E.Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States (author)
Rabe, Kari G.Department of Quantitative Health Sciences, Mayo Clinic College of Medicine, MN, Rochester, United States (author)
Bamlet, William R.Department of Quantitative Health Sciences, Mayo Clinic College of Medicine, MN, Rochester, United States (author)
Chanock, Stephen J.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Fuchs, Charles S.Yale Cancer Center, CT, New Haven, United States; Department of Medicine, Yale School of Medicine, CT, New Haven, United States; Smilow Cancer Hospital, CT, New Haven, United States (author)
Gaziano, J MichaelDivision of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States; Boston Veteran Affairs Healthcare System, MA, Boston, United States (author)
Giovannucci, Edward L.Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States (author)
Hackert, ThiloDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany (author)
Hassan, Manal M.Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, TX, Houston, United States (author)
Katzke, VerenaDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (author)
Kurtz, Robert C.Gastroenterology, Hepatology, Nutrition Service, Memorial Sloan Kettering Cancer Center, NY, United States (author)
Lee, I-MinDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States (author)
Malats, NúriaGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain (author)
Murphy, NeilSection of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (author)
Oberg, Ann L.Department of Quantitative Health Sciences, Mayo Clinic College of Medicine, MN, Rochester, United States (author)
Orlow, IreneDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, NY, United States (author)
Porta, MiquelHospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Spain (author)
Real, Francisco X.Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, Madrid, Spain (author)
Rothman, NathanielDivision of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Sesso, Howard D.Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States (author)
Silverman, Debra T.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Thompson, Ian M.CHRISTUS Santa Rosa Hospital - Medical Center, TX, San Antonio, United States (author)
Wactawski-Wende, JeanDepartment of Epidemiology and Environmental Health, University of Buffalo, NY, Buffalo, United States (author)
Wang, XiaoliangCancer Prevention Program, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Wentzensen, NicolasDivision of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Yu, HerbertCancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, HI, Honolulu, United States (author)
Zeleniuch-Jacquotte, AnneDepartments of Population Health and Environmental Medicine, NYU Perlmutter Comprehensive Cancer Center, NY, United States (author)
Yu, KaiDivision of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Wolpin, Brian M.Department of Medical Oncology, Dana-Farber Cancer Institute, MA, Boston, United States (author)
Duell, Eric J.Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain (author)
Li, DonghuiDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, TX, Houston, United States (author)
Hung, Rayjean J.Lunenfeld-Tanenbaum Research Institute of Sinai Health System, University of Toronto, Toronto, Canada (author)
Perdomo, SandraGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France (author)
McCullough, Marjorie L.Department of Population Science, American Cancer Society, Atlanta, Georgia (author)
Freedman, Neal D.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Patel, Alpa V.Department of Population Science, American Cancer Society, Atlanta, Georgia (author)
Peters, UlrikeDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (author)
Riboli, ElioDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States (author)
Sund, MalinUmeå universitet,Institutionen för kirurgisk och perioperativ vetenskap(Swepub:umu)masu0021 (author)
Tjønneland, AnneDanish Cancer Society Research Center, Copenhagen, Denmark (author)
Zhong, JunDivision of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Van Den Eeden, Stephen K.Division of Research, Northern California, Kaiser Permanente, CA, Oakland, United States; Department of Urology, University of California San Francisco, CA, San Francisco, United States (author)
Kraft, PeterDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States (author)
Risch, Harvey A.Department of Chronic Disease Epidemiology, Yale School of Public Health, CT, New Haven, United States (author)
Amundadottir, Laufey T.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Klein, Alison P.Department of Epidemiology, Johns Hopkins School of Public Health, MD, Baltimore, Liberia; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, MD, Baltimore, Liberia; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, MD, Baltimore, Liberia (author)
Stolzenberg-Solomon, Rachael Z.Division of Cancer Epidemiology and Genetics, NCI, NIH, MD, Bethesda, Liberia (author)
Antwi, Samuel O.Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, FL, Jacksonville, Puerto Rico; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, FL, Jacksonville, Puerto Rico (author)
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, FL, Jacksonville, Puerto RicoDivision of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, FL, Jacksonville, Puerto Rico (creator_code:org_t)

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In:Cancer Epidemiology, Biomarkers and Prevention: American Association For Cancer Research (AACR)32:9, s. 1265-12691055-99651538-7755

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By the author/editor: King, Sontoria D ...; Veliginti, Swath ...; Brouwers, Martij ...; Ren, Zhewen; Zheng, Wei; Setiawan, Veroni ...; show more...; Wilkens, Lynne R ...; Shu, Xiao-Ou; Arslan, Alan A.; Beane Freeman, L ...; Bracci, Paige M.; Canzian, Federic ...; Du, Mengmeng; Gallinger, Steve ...; Giles, Graham G.; Goodman, Phyllis ...; Haiman, Christop ...; Kogevinas, Manol ...; Kooperberg, Char ...; LeMarchand, Loic; Neale, Rachel E.; Visvanathan, Kal ...; White, Emily; Albanes, Demetri ...; Andreotti, Gabri ...; Babic, Ana; Berndt, Sonja I.; Brais, Lauren K.; Brennan, Paul; Buring, Julie E.; Rabe, Kari G.; Bamlet, William ...; Chanock, Stephen ...; Fuchs, Charles S ...; Gaziano, J Micha ...; Giovannucci, Edw ...; Hackert, Thilo; Hassan, Manal M.; Katzke, Verena; Kurtz, Robert C.; Lee, I-Min; Malats, Núria; Murphy, Neil; Oberg, Ann L.; Orlow, Irene; Porta, Miquel; Real, Francisco ...; Rothman, Nathani ...; Sesso, Howard D.; Silverman, Debra ...; Thompson, Ian M.; Wactawski-Wende, ...; Wang, Xiaoliang; Wentzensen, Nico ...; Yu, Herbert; Zeleniuch-Jacquo ...; Yu, Kai; Wolpin, Brian M.; Duell, Eric J.; Li, Donghui; Hung, Rayjean J.; Perdomo, Sandra; McCullough, Marj ...; Freedman, Neal D ...; Patel, Alpa V.; Peters, Ulrike; Riboli, Elio; Sund, Malin; Tjønneland, Anne; Zhong, Jun; Van Den Eeden, S ...; Kraft, Peter; Risch, Harvey A.; Amundadottir, La ...; Klein, Alison P.; Stolzenberg-Solo ...; Antwi, Samuel O.; show less...

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