Web of Science: 53 cites, Scopus: 60 cites, Google Scholar: cites,
Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
Zhang, Mingfeng (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Wang, Zhaoming (Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA)
Obazee, Ofure (Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany)
Jia, Jinping (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Childs, Erica J. (Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA)
Hoskins, Jason (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Figlioli, Gisella (Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany)
Mocci, Evelina (Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA)
Collins, Irene (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Chung, Charles C. (Frederick National Laboratory for Cancer Research (Frederick, Estats Units d'Amèrica))
Hautman, Christopher (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Arslan, Alan A. (New York University Cancer Institute, New York, New York, USA)
Beane-Freeman, Laura (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Bracci, Paige M. (Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA)
Buring, Julie (Harvard Medical School)
Duell, Eric J. (Institut d'Investigació Biomèdica de Bellvitge)
Gallinger, Steven (Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada)
Giles, Graham G. (Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia)
Goodman, Gary E. (Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)
Goodman, Phyllis J. (Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)
Kamineni, Aruna (Group Health Research Institute, Seattle, Washington, USA)
Kolonel, Laurence N. (Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA)
Kulke, Matthew H. (Dana-Farber Cancer Institute (Boston, Estats Units d'Amèrica). Department of Medical Oncology)
Malats, Núria (Centro Nacional de Investigaciones Oncológicas)
Olson, Sara H. (Memorial Sloan Kettering Cancer Center)
Sesso, Howard D. (Harvard Medical School)
Visvanathan, Kala (Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA)
White, Emily (Department of Epidemiology, University of Washington, Seattle, Washington, USA)
Zheng, Wei (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA)
Abnet, Christian C. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Albanes, Demetrius (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Andreotti, Gabriella (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Brais, Lauren (Dana-Farber Cancer Institute (Boston, Estats Units d'Amèrica). Department of Medical Oncology)
Bueno-de-Mesquita, H. Bas (Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia)
Basso, Daniela (Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy)
Berndt, Sonja I. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Boutron-Ruault, Marie-Christine (IGR, F-94805, Villejuif, France)
Bijlsma, Maarten F. (Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands)
Brenner, Hermann (German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany)
Burdette, Laurie (Frederick National Laboratory for Cancer Research (Frederick, Estats Units d'Amèrica))
Campa, Daniele (Department of Biology, University of Pisa, Pisa, Italy)
Caporaso, Neil E. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Capurso, Gabriele (Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy)
Cavestro, Giulia Martina (Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy)
Cotterchio, Michelle (University of Toronto. Dalla Lana School of Public Health)
Costello, Eithne (National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom)
Elena, Joanne (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Boggi, Ugo (Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy)
Gaziano, J. Michael (Massachusetts Veteran's Epidemiology, Research, and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA)
Gazouli, Maria (Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece)
Giovannucci, Edward L. (Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA)
Goggins, Michael (Department of Oncology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA)
Gross, Myron (Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA)
Haiman, Christopher A. (Preventive Medicine, University of Southern California, Los Angeles, California, USA)
Hassan, Manal (Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA)
Helzlsouer, Kathy J. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Hu, Nan (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Hunter, David J. (Harvard Medical School, Boston, Massachusetts, USA)
Iskierka-Jazdzewska, Elzbieta (Department of Hematology, Medical University of Łodz, Łodz, Poland)
Jenab, Mazda (International Agency for Research on Cancer (IARC), Lyon, France)
Kaaks, Rudolf (Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany)
Key, Timothy J. (Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom)
Khaw, Kay-Tee (School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom)
Klein, Eric A. (Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA)
Kogevinas, M (Institut Hospital del Mar d'Investigacions Mèdiques)
Krogh, Vittorio (Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy)
Kupcinskas, Juozas (Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania)
Kurtz, Robert C. (Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA)
Landi, Maria T. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Landi, Stefano (Department of Biology, University of Pisa, Pisa, Italy)
Marchand, Le Loic (Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA)
Mambrini, Andrea (Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy)
Mannisto, Satu (National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland)
Milne, Roger L. (Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia)
Neale, Rachel E. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Oberg, Ann L. (Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA)
Panico, Salvatore (Dipartimento di Medicina Clinica E Chirurgia, Federico II Univeristy, Naples, Italy)
Patel, Alpa V. (Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA)
Peeters, Petra H. M. (Imperial College London. Department of Epidemiology and Biostatistics)
Peters, Ulrike (Department of Epidemiology, University of Washington, Seattle, Washington, USA)
Pezzilli, Raffaele (Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy)
Porta, Miquel (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i Medicina Preventiva i Salut Pública)
Purdue, Mark (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Quiros, J. Ramón (Public Health and Participation Directorate, Asturias, Spain)
Riboli, Elio (Imperial College London. Department of Epidemiology and Biostatistics)
Rothman, Nathaniel (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Scarpa, Aldo (University and Hospital Trust of Verona. ARC-Net Centre for Applied Research on Cancer)
Scelo, Ghislaine (International Agency for Research on Cancer (IARC), Lyon, France)
Shu, Xiao-Ou (Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA)
Silverman, Debra T. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Soucek, Pavel (Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic)
Strobel, Oliver (Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany)
Sund, Malin (Department of Surgical and Peroperative Sciences, Umeå University, Umeå, Sweden)
Małecka-Panas, Ewa (Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland)
Taylor, Philip R. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Tavano, Francesca (Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy)
Travis, Ruth C. (Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom)
Thornquist, Mark (Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)
Tjønneland, Anne (Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark)
Tobias, Geoffrey S. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Trichopoulos, Dimitrios (Hellenic Health Foundation, Athens, Greece)
Vashist, Yogesh (Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, Hamburg, Germany)
Vodicka, Pavel (Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic)
Wactawski-Wende, Jean (Department of Social and Preventive Medicine, University at Buffalo, Buffalo, New York, USA)
Wentzensen, Nicolas (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Yu, Herbert (Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA)
Yu, Kai (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Zeleniuch-Jacquotte, Anne (New York University Cancer Institute, New York, New York, USA)
Kooperberg, Charles (Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)
Risch, Harvey A. (Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA)
Jacobs, Eric J. (Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA)
Li, Donghui (Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA)
Fuchs, Charles (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Hoover, Robert (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Hartge, Patricia (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Chanock, Stephen J. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Petersen, Gloria M. (Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA)
Stolzenberg-Solomon, Rachael S. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))
Wolpin, Brian M. (Dana-Farber Cancer Institute (Boston, Estats Units d'Amèrica). Department of Medical Oncology)
Kraft, Peter (Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA)
Klein, Alison P. (Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland, USA)
Canzian, Federico (Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany)
Amundadottir, Laufey T. (National Cancer Institute (Bethesda, Estats Units d'Amèrica))

Data: 2016
Resum: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32. 1 (per allele odds ratio (OR) = 1. 20, P = 4. 88×10 −15), rs10094872 at 8q24. 21 (OR = 1. 15, P = 3. 22×10 −9) and rs35226131 at 5p15. 33 (OR = 0. 71, P = 1. 70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32. 1 (NR5A2), chr8q24. 21 (MYC) and chr5p15. 33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32. 1) in the tumors (fold change -7. 6, P = 5. 7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31. 3 to -95. 7, P = 7. 5×10 −4 -2. 0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
Nota: Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Pancreatic cancer ; GWAS ; Fine-mapping ; Imputation ; NR5A2
Publicat a: Oncotarget, Vol. 7 (august 2016) , p. 66328-66343, ISSN 1949-2553

DOI: 10.18632/oncotarget.11041
PMID: 27579533


16 p, 3.1 MB

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