Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies.

Autor:	Julián-Serrano S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Yuan F; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Wheeler W; Information Management Services, Silver Spring, MD, USA., Benyamin B; Australian Centre for Precision Health, Allied Health and Human Performance, University of South Australia, Adelaide, Australia.; South Australian Health and Medical Research Institute, Adelaide, Australia., Machiela MJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Arslan AA; Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA., Beane-Freeman LE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Bracci PM; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Duell EJ; Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain., Du M; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gallinger S; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Giles GG; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia., Goodman PJ; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Kooperberg C; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Marchand LL; Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, USA., Neale RE; Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia., Shu XO; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Van Den Eeden SK; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Visvanathan K; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Albanes D; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Andreotti G; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Ardanaz E; Navarra Public Health Institute, Pamplona, Spain.; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain., Babic A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Brais LK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Brennan P; International Agency for Research on Cancer (IARC), Lyon, France., Bueno-de-Mesquita B; Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands., Buring JE; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Childs EJ; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA., Chung CC; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Fabiánová E; Specialized Institute of Hygiene and Epidemiology, Banska Bystrica, Slovakia., Foretová L; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic., Fuchs CS; Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT, USA., Gaziano JM; Division of Aging, Brigham and Women's Hospital, Boston, MA, USA., Gentiluomo M; Department of Biology, University of Pisa, Italy.; Genomic Epidemiology Group, German Cancer Research Center, (DKFZ), Heidelberg, Germany., Giovannucci EL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Goggins MG; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Hackert T; Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany., Hartge P; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Hassan MM; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Holcátová I; Institute of Public Health and Preventive Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic., Holly EA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Hung RI; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Janout V; Faculty of Health Sciences, University of Olomouc, Olomouc, Czech Republic., Kurtz RC; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Lee IM; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Malats N; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., McKean D; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA., Milne RL; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia., Newton CC; Department of Population Science, American Cancer Society, Atlanta, GA, USA., Oberg AL; Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA., Perdomo S; International Agency for Research on Cancer (IARC), Lyon, France., Peters U; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Porta M; Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain., Rothman N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Schulze MB; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany., Sesso HD; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Silverman DT; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Thompson IM; CHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, TX, USA., Wactawski-Wende J; Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA., Weiderpass E; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Wenstzensen N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., White E; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Wilkens LR; Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, USA., Yu H; Department of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, USA., Zeleniuch-Jacquotte A; Department of Population Health and Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA., Zhong J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Li D; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Campbell PT; Department of Population Science, American Cancer Society, Atlanta, GA, USA., Petersen GM; Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA., Wolpin BM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Risch HA; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA., Amundadottir LT; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Klein AP; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Yu K; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Stolzenberg-Solomon RZ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Jazyk:	angličtina
Zdroj:	The American journal of clinical nutrition [Am J Clin Nutr] 2021 Oct 04; Vol. 114 (4), pp. 1408-1417.
DOI:	10.1093/ajcn/nqab217
Abstrakt:	Background: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. Objectives: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. Methods: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. Results: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. Conclusions: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association. (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)
Databáze:	MEDLINE
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