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Pancreatic Neoplasms: HELP
Articles by Melissa A. Austin
Based on 9 articles published since 2009
(Why 9 articles?)
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Between 2009 and 2019, Melissa Austin wrote the following 9 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. 2015

Campa, Daniele / Rizzato, Cosmeri / Stolzenberg-Solomon, Rachael / Pacetti, Paola / Vodicka, Pavel / Cleary, Sean P / Capurso, Gabriele / Bueno-de-Mesquita, H B As / Werner, Jens / Gazouli, Maria / Butterbach, Katja / Ivanauskas, Audrius / Giese, Nathalia / Petersen, Gloria M / Fogar, Paola / Wang, Zhaoming / Bassi, Claudio / Ryska, Miroslav / Theodoropoulos, George E / Kooperberg, Charles / Li, Donghui / Greenhalf, William / Pasquali, Claudio / Hackert, Thilo / Fuchs, Charles S / Mohelnikova-Duchonova, Beatrice / Sperti, Cosimo / Funel, Niccola / Dieffenbach, Aida Karina / Wareham, Nicholas J / Buring, Julie / Holcátová, Ivana / Costello, Eithne / Zambon, Carlo-Federico / Kupcinskas, Juozas / Risch, Harvey A / Kraft, Peter / Bracci, Paige M / Pezzilli, Raffaele / Olson, Sara H / Sesso, Howard D / Hartge, Patricia / Strobel, Oliver / Małecka-Panas, Ewa / Visvanathan, Kala / Arslan, Alan A / Pedrazzoli, Sergio / Souček, Pavel / Gioffreda, Domenica / Key, Timothy J / Talar-Wojnarowska, Renata / Scarpa, Aldo / Mambrini, Andrea / Jacobs, Eric J / Jamroziak, Krzysztof / Klein, Alison / Tavano, Francesca / Bambi, Franco / Landi, Stefano / Austin, Melissa A / Vodickova, Ludmila / Brenner, Hermann / Chanock, Stephen J / Delle Fave, Gianfranco / Piepoli, Ada / Cantore, Maurizio / Zheng, Wei / Wolpin, Brian M / Amundadottir, Laufey T / Canzian, Federico. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. · Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy. · Surgical and Oncological Department, Pancreas Institute - University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Second Faculty of Medicine, Charles University in Prague and Central Military Hospital, Prague, Czech Republic. · 1st Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of Surgery, Gastroenterology and Oncology (DISCOG), University of Padua, Padua, Italy. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. · Department of Oncology, Palacky University Medical School and Teaching Hospital in Olomouc, Olomouc, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · German Cancer Consortium (DKTK), Heidelberg, Germany. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. · Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padua, Padua, Italy. · Department of Epidemiology and Public Health, Yale School of Public Health, New Haven, CT. · Department of Epidemiology, Harvard School of Public Health, Boston, MA. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. · Division of Epidemiology, Departments of Obstetrics and Gynecology, Environmental Medicine, and Population Health, New York University School of Medicine, New York, NY. · Surgical Clinic 4, University of Padua, Padua, Italy. · Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo Della Sofferenza,", San Giovanni Rotondo, Italy. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, GA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Epidemiology, University of Washington, Seattle, WA. · Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN. ·Int J Cancer · Pubmed #25940397.

ABSTRACT: A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

2 Article Vitamin D metabolic pathway genes and pancreatic cancer risk. 2015

Arem, Hannah / Yu, Kai / Xiong, Xiaoqin / Moy, Kristin / Freedman, Neal D / Mayne, Susan T / Albanes, Demetrius / Arslan, Alan A / Austin, Melissa / Bamlet, William R / Beane-Freeman, Laura / Bracci, Paige / Canzian, Federico / Cotterchio, Michelle / Duell, Eric J / Gallinger, Steve / Giles, Graham G / Goggins, Michael / Goodman, Phyllis J / Hartge, Patricia / Hassan, Manal / Helzlsouer, Kathy / Henderson, Brian / Holly, Elizabeth A / Hoover, Robert / Jacobs, Eric J / Kamineni, Aruna / Klein, Alison / Klein, Eric / Kolonel, Laurence N / Li, Donghui / Malats, Núria / Männistö, Satu / McCullough, Marjorie L / Olson, Sara H / Orlow, Irene / Peters, Ulrike / Petersen, Gloria M / Porta, Miquel / Severi, Gianluca / Shu, Xiao-Ou / Visvanathan, Kala / White, Emily / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Zheng, Wei / Tobias, Geoffrey S / Maeder, Dennis / Brotzman, Michelle / Risch, Harvey / Sampson, Joshua N / Stolzenberg-Solomon, Rachael Z. ·Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. · Information Management Systems, Inc., Calverton, Maryland, United States of America. · Yale School of Public Health/Yale Cancer Center, New Haven, Connecticut, United States of America. · Departments of Population Health, Obstetrics and Gynecology (Obs/Gyn) and Environmental Medicine, New York University, New York, New York, United States of America. · Department of Epidemiology, University of Washington, Seattle, Washington, United States of America. · Department of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Dalla Lana School of Public Health, University of Toronto; Prevention and Cancer Control, Cancer Care Ontario Toronto, Ontario, Canada. · Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Cancer Epidemiology Centre, Cancer Council Victoria and Centre for MEGA Epidemiology, School of Population Health, the University of Melbourne, Melbourne, Australia. · Departments of Oncology, Pathology and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. · Cleveland Clinic, Glickman Urological and Kidney Institute, Cleveland, Ohio, United States of America. · Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America. · MD Mercy, Baltimore, Maryland, United States of America. · Department of Preventative Medicine, School of Medicine, University of Southern California, Los Angeles, California, United States of America. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America. · GroupHealth Research Institute, Seattle, Washington, United States of America. · University of Hawaii Cancer Center, Manoa, Hawaii, United States of America. · Molecular Pathology Program, Spanish National Cancer Research Center, Madrid, Spain. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. · Hospital del Mar Institute of Medical Research (IMIM), and School of Medicine, Barcelona Spain. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, United States of America. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America. · Westat, Rockville, Maryland, United States of America. ·PLoS One · Pubmed #25799011.

ABSTRACT: Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

3 Article Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. 2014

Wolpin, Brian M / Rizzato, Cosmeri / Kraft, Peter / Kooperberg, Charles / Petersen, Gloria M / Wang, Zhaoming / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Canzian, Federico / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E / Goodman, Phyllis J / Jacobs, Eric J / Kamineni, Aruna / Klein, Alison P / Kolonel, Laurence N / Kulke, Matthew H / Li, Donghui / Malats, Núria / Olson, Sara H / Risch, Harvey A / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Austin, Melissa A / Barfield, Richard / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Brotzman, Michelle / Büchler, Markus W / Bueno-de-Mesquita, H Bas / Bugert, Peter / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Chung, Charles / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Funel, Niccola / Gaziano, J Michael / Giese, Nathalia A / Giovannucci, Edward L / Goggins, Michael / Gorman, Megan J / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Henderson, Brian E / Holly, Elizabeth A / Hu, Nan / Hunter, David J / Innocenti, Federico / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / LaCroix, Andrea / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Nakamura, Yusuke / Oberg, Ann L / Owzar, Kouros / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Piepoli, Ada / Porta, Miquel / Real, Francisco X / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Sund, Malin / Talar-Wojnarowska, Renata / Taylor, Philip R / Theodoropoulos, George E / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Wu, Chen / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Hoover, Robert / Hartge, Patricia / Fuchs, Charles / Chanock, Stephen J / Stolzenberg-Solomon, Rachael S / Amundadottir, Laufey T. ·1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3]. · 1] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2]. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3]. · 1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2]. · 1] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [2]. · 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. · 1] Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. [2] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [3] New York University Cancer Institute, New York, New York, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. · 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. [3] Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Group Health Research Institute, Seattle, Washington, USA. · 1] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, USA. · The Cancer Research Center of Hawaii (retired), Honolulu, Hawaii, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Genetic and Molecular Epidemiology Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · 1] Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA. · 1] Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy. · 1] INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif, France. [2] University Paris Sud, UMRS 1018, Villejuif, France. [3] Institut Gustave Roussy (IGR), Villejuif, France. · Westat, Rockville, Maryland, USA. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · 1] National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [2] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands. [3] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. · Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany. · Division of Cancer Epidemiology, DKFZ, Heidelberg, Germany. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · 1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, UK. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · 1] Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [2] Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [3] Department of Oncology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. · Preventive Medicine, University of Southern California, Los Angeles, California, USA. · Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA. · Cancer Prevention, University of Southern California, Los Angeles, California, USA. · 1] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Harvard School of Public Health, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. · The University of North Carolina Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, School of Medicine, Chapel Hill, North Carolina, USA. · International Agency for Research on Cancer, Lyon, France. · Cancer Epidemiology Unit, University of Oxford, Oxford, UK. · School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA. · 1] Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [2] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [3] Department of Nutrition, National School of Public Health, Athens, Greece. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Department of Biology, University of Pisa, Pisa, Italy. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. · 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. · Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. · Alliance Statistics and Data Center, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Alliance Statistics and Data Center, Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA. · 1] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. [2] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Department of Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Gastroenterology, Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo, Italy. · 1] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [2] Department of Epidemiology, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. [3] CIBERESP, Madrid, Spain. · 1] Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. [2] Departament de Ciències i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Toxicogenomics Unit, Center for Toxicology and Safety, National Institute of Public Health, Prague, Czech Republic. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · 1st Propaideutic Surgical Department, Hippocration University Hospital, Athens, Greece. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [3] Hellenic Health Foundation, Athens, Greece. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. · Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · 1] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [2] New York University Cancer Institute, New York, New York, USA. · 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2]. · 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3]. · 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. [3]. ·Nat Genet · Pubmed #25086665.

ABSTRACT: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

4 Article Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. 2014

Wang, Zhaoming / Zhu, Bin / Zhang, Mingfeng / Parikh, Hemang / Jia, Jinping / Chung, Charles C / Sampson, Joshua N / Hoskins, Jason W / Hutchinson, Amy / Burdette, Laurie / Ibrahim, Abdisamad / Hautman, Christopher / Raj, Preethi S / Abnet, Christian C / Adjei, Andrew A / Ahlbom, Anders / Albanes, Demetrius / Allen, Naomi E / Ambrosone, Christine B / Aldrich, Melinda / Amiano, Pilar / Amos, Christopher / Andersson, Ulrika / Andriole, Gerald / Andrulis, Irene L / Arici, Cecilia / Arslan, Alan A / Austin, Melissa A / Baris, Dalsu / Barkauskas, Donald A / Bassig, Bryan A / Beane Freeman, Laura E / Berg, Christine D / Berndt, Sonja I / Bertazzi, Pier Alberto / Biritwum, Richard B / Black, Amanda / Blot, William / Boeing, Heiner / Boffetta, Paolo / Bolton, Kelly / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Brennan, Paul / Brinton, Louise A / Brotzman, Michelle / Bueno-de-Mesquita, H Bas / Buring, Julie E / Butler, Mary Ann / Cai, Qiuyin / Cancel-Tassin, Geraldine / Canzian, Federico / Cao, Guangwen / Caporaso, Neil E / Carrato, Alfredo / Carreon, Tania / Carta, Angela / Chang, Gee-Chen / Chang, I-Shou / Chang-Claude, Jenny / Che, Xu / Chen, Chien-Jen / Chen, Chih-Yi / Chen, Chung-Hsing / Chen, Constance / Chen, Kuan-Yu / Chen, Yuh-Min / Chokkalingam, Anand P / Chu, Lisa W / Clavel-Chapelon, Francoise / Colditz, Graham A / Colt, Joanne S / Conti, David / Cook, Michael B / Cortessis, Victoria K / Crawford, E David / Cussenot, Olivier / Davis, Faith G / De Vivo, Immaculata / Deng, Xiang / Ding, Ti / Dinney, Colin P / Di Stefano, Anna Luisa / Diver, W Ryan / Duell, Eric J / Elena, Joanne W / Fan, Jin-Hu / Feigelson, Heather Spencer / Feychting, Maria / Figueroa, Jonine D / Flanagan, Adrienne M / Fraumeni, Joseph F / Freedman, Neal D / Fridley, Brooke L / Fuchs, Charles S / Gago-Dominguez, Manuela / Gallinger, Steven / Gao, Yu-Tang / Gapstur, Susan M / Garcia-Closas, Montserrat / Garcia-Closas, Reina / Gastier-Foster, Julie M / Gaziano, J Michael / Gerhard, Daniela S / Giffen, Carol A / Giles, Graham G / Gillanders, Elizabeth M / Giovannucci, Edward L / Goggins, Michael / Gokgoz, Nalan / Goldstein, Alisa M / Gonzalez, Carlos / Gorlick, Richard / Greene, Mark H / Gross, Myron / Grossman, H Barton / Grubb, Robert / Gu, Jian / Guan, Peng / Haiman, Christopher A / Hallmans, Goran / Hankinson, Susan E / Harris, Curtis C / Hartge, Patricia / Hattinger, Claudia / Hayes, Richard B / He, Qincheng / Helman, Lee / Henderson, Brian E / Henriksson, Roger / Hoffman-Bolton, Judith / Hohensee, Chancellor / Holly, Elizabeth A / Hong, Yun-Chul / Hoover, Robert N / Hosgood, H Dean / Hsiao, Chin-Fu / Hsing, Ann W / Hsiung, Chao Agnes / Hu, Nan / Hu, Wei / Hu, Zhibin / Huang, Ming-Shyan / Hunter, David J / Inskip, Peter D / Ito, Hidemi / Jacobs, Eric J / Jacobs, Kevin B / Jenab, Mazda / Ji, Bu-Tian / Johansen, Christoffer / Johansson, Mattias / Johnson, Alison / Kaaks, Rudolf / Kamat, Ashish M / Kamineni, Aruna / Karagas, Margaret / Khanna, Chand / Khaw, Kay-Tee / Kim, Christopher / Kim, In-Sam / Kim, Jin Hee / Kim, Yeul Hong / Kim, Young-Chul / Kim, Young Tae / Kang, Chang Hyun / Jung, Yoo Jin / Kitahara, Cari M / Klein, Alison P / Klein, Robert / Kogevinas, Manolis / Koh, Woon-Puay / Kohno, Takashi / Kolonel, Laurence N / Kooperberg, Charles / Kratz, Christian P / Krogh, Vittorio / Kunitoh, Hideo / Kurtz, Robert C / Kurucu, Nilgun / Lan, Qing / Lathrop, Mark / Lau, Ching C / Lecanda, Fernando / Lee, Kyoung-Mu / Lee, Maxwell P / Le Marchand, Loic / Lerner, Seth P / Li, Donghui / Liao, Linda M / Lim, Wei-Yen / Lin, Dongxin / Lin, Jie / Lindstrom, Sara / Linet, Martha S / Lissowska, Jolanta / Liu, Jianjun / Ljungberg, Börje / Lloreta, Josep / Lu, Daru / Ma, Jing / Malats, Nuria / Mannisto, Satu / Marina, Neyssa / Mastrangelo, Giuseppe / Matsuo, Keitaro / McGlynn, Katherine A / McKean-Cowdin, Roberta / McNeill, Lorna H / McWilliams, Robert R / Melin, Beatrice S / Meltzer, Paul S / Mensah, James E / Miao, Xiaoping / Michaud, Dominique S / Mondul, Alison M / Moore, Lee E / Muir, Kenneth / Niwa, Shelley / Olson, Sara H / Orr, Nick / Panico, Salvatore / Park, Jae Yong / Patel, Alpa V / Patino-Garcia, Ana / Pavanello, Sofia / Peeters, Petra H M / Peplonska, Beata / Peters, Ulrike / Petersen, Gloria M / Picci, Piero / Pike, Malcolm C / Porru, Stefano / Prescott, Jennifer / Pu, Xia / Purdue, Mark P / Qiao, You-Lin / Rajaraman, Preetha / Riboli, Elio / Risch, Harvey A / Rodabough, Rebecca J / Rothman, Nathaniel / Ruder, Avima M / Ryu, Jeong-Seon / Sanson, Marc / Schned, Alan / Schumacher, Fredrick R / Schwartz, Ann G / Schwartz, Kendra L / Schwenn, Molly / Scotlandi, Katia / Seow, Adeline / Serra, Consol / Serra, Massimo / Sesso, Howard D / Severi, Gianluca / Shen, Hongbing / Shen, Min / Shete, Sanjay / Shiraishi, Kouya / Shu, Xiao-Ou / Siddiq, Afshan / Sierrasesumaga, Luis / Sierri, Sabina / Loon Sihoe, Alan Dart / Silverman, Debra T / Simon, Matthias / Southey, Melissa C / Spector, Logan / Spitz, Margaret / Stampfer, Meir / Stattin, Par / Stern, Mariana C / Stevens, Victoria L / Stolzenberg-Solomon, Rachael Z / Stram, Daniel O / Strom, Sara S / Su, Wu-Chou / Sund, Malin / Sung, Sook Whan / Swerdlow, Anthony / Tan, Wen / Tanaka, Hideo / Tang, Wei / Tang, Ze-Zhang / Tardon, Adonina / Tay, Evelyn / Taylor, Philip R / Tettey, Yao / Thomas, David M / Tirabosco, Roberto / Tjonneland, Anne / Tobias, Geoffrey S / Toro, Jorge R / Travis, Ruth C / Trichopoulos, Dimitrios / Troisi, Rebecca / Truelove, Ann / Tsai, Ying-Huang / Tucker, Margaret A / Tumino, Rosario / Van Den Berg, David / Van Den Eeden, Stephen K / Vermeulen, Roel / Vineis, Paolo / Visvanathan, Kala / Vogel, Ulla / Wang, Chaoyu / Wang, Chengfeng / Wang, Junwen / Wang, Sophia S / Weiderpass, Elisabete / Weinstein, Stephanie J / Wentzensen, Nicolas / Wheeler, William / White, Emily / Wiencke, John K / Wolk, Alicja / Wolpin, Brian M / Wong, Maria Pik / Wrensch, Margaret / Wu, Chen / Wu, Tangchun / Wu, Xifeng / Wu, Yi-Long / Wunder, Jay S / Xiang, 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Hospital, Toronto, ON, Canada. · Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain. · Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY, USA. · Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA. · Department of Urology, Washington University School of Medicine, St Louis, MO, USA. · Department of Epidemiology. · Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. · Department of Public Health and Clinical Medicine/Nutritional Research. · Channing Laboratory, Department of Medicine. · Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. · Laboratory of Experimental Oncology, Orthopaedic 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Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. · Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea. · Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. · Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Department of Medicine and. · Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, National School of Public Health, Athens, Greece. · Duke-NUS Graduate Medical School, Singapore, Singapore, Saw Swee Hock School of 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Singapore, Singapore, School of Life Sciences, Anhui Medical University, Hefei, China. · Department of Surgical and Perioperative Sciences, Urology and Andrology and. · CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. · Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. · Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Centro Nacional de Investigaciones Oncologicas, Melchor Fernández Almagro, 3, Madrid E-28029, Spain. · National Institute for Health and Welfare, Helsinki, Finland. · Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA. · Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padua, Italy. · Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan, Department of Preventive Medicine, Kyushu University Faculty of Medical Scicence, Fukuoka, Japan. · Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, and Center for Community-Engaged Translational Research, Duncan Family Institute and. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. · Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, RI, USA. · Health Sciences Research Institute, University of Warwick, Coventry, UK. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Complex Traits Genetics Team and. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. · Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Utrecht, The Netherlands, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Nofer Institute of Occupational Medicine, Lodz, Poland. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Yale School of Public Health, New Haven, CT, USA. · Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea. · Karmanos Cancer Institute and Department of Oncology and. · Karmanos Cancer Institute and Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA. · Maine Cancer Registry, Augusta, ME, USA. · Centre for Research in Occupational Health, Universitat Pompeu Fabra, Barcelona, Spain, CIBER of Epidemiology and Public Health (CIBERESP). · Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA. · Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK. · Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Surgery, Division of Cardiothoracic Surgery, Queen Mary Hospital, Hong Kong, China. · Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany. · Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia. · University of Minnesota, Minneapolis, MN, USA. · Dan L. Duncan Center, Baylor College of Medicine, Houston, TX, USA. · Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. · Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden. · Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, Seoul, South Korea. · Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK, Division of Breast Cancer Research, Institute of Cancer Research, London, UK. · Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain. · Sir Peter MacCallum Department of Oncology, University of Melbourne, St Andrew's Place, East Melbourne, VIC, Australia. · Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. · Department of Pulmonary Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan. · Cancer Registry Associazione Iblea Ricerca Epidemiologica, Onlus and Asp Ragusa, Ragusa Italy. · Kaiser Permanente Northern California, Oakland, CA, USA. · Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. · Imperial College, London, UK, Human Genetics Foundation (HuGeF), Torino Italy. · National Research Centre for the Working Environment, Copenhagen, Denmark, National Food Institute, Technical University of Denmark, Soborg, Denmark. · Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. · Division of Cancer Etiology, Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, CA, USA. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Department of Research, Cancer Registry of Norway, Oslo, Norway, Department of Medical Epidemiology and Biostatistics and Samfundet Folkhälsan, Helsinki, Finland. · University of California San Francisco, San Francisco, CA, USA. · Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Pathology and. · Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. · School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China. · Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital and. · University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA and. · Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA. · Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. · Division of Cancer Epidemiology and Genetics, amundadottirl@mail.nih.gov. ·Hum Mol Genet · Pubmed #25027329.

ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

5 Article Family history of diabetes and pancreatic cancer as risk factors for pancreatic cancer: the PACIFIC study. 2013

Austin, Melissa A / Kuo, Elena / Van Den Eeden, Stephen K / Mandelson, Margaret T / Brentnall, Teresa A / Kamineni, Aruna / Potter, John D. ·Authors' Affiliations: Departments of Epidemiology and Gastroenterology, University of Washington; Group Health Research Institute and Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Research, Kaiser Permanente Northern California, Oakland, California; and Centre for Public Health Research, Massey University, Wellington, New Zealand. ·Cancer Epidemiol Biomarkers Prev · Pubmed #23966578.

ABSTRACT: Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying individuals at high risk for this disease. The goal of this analysis was to evaluate associations of family history of diabetes and family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a case-control study based on two large health plans. Cases were diagnosed with pancreatic ductal adenocarcinoma (PDA) and controls were selected from the health plan enrollment databases and frequency matched to cases. Family history data were collected using an interviewer-administered questionnaire and were available on 654 cases and 697 controls. Logistic regression was used for the association analyses. First-degree relative history of diabetes was statistically significantly associated with increased risk of PDA [OR, 1.37; 95% confidence interval (CI), 1.10-1.71]. The highest risk of PDA was observed for an offspring with diabetes (OR, 1.95; 95% CI, 1.23-3.09). In addition, history of pancreatic cancer increased risk for PDA with an OR of 2.79 (95% CI, 1.44-4.08) for any first-degree relative history of pancreatic cancer. This population-based analysis showed that family history of diabetes was associated with increased risk of PDA and confirmed previous studies showing that first-degree family history of pancreatic cancer is associated with PDA. These results support the need for ongoing studies of genetic influences on pancreatic cancer in large samples and investigations of possible pleiotropic genetic effects on diabetes and pancreatic cancer.

6 Article Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data. 2011

Pierce, Brandon L / Austin, Melissa A / Ahsan, Habibul. ·Department of Health Studies and Comprehensive Cancer Center, The University of Chicago, IL, 60637, USA. brandonpierce@uchicago.edu ·Cancer Causes Control · Pubmed #21445555.

ABSTRACT: OBJECTIVE: To examine associations between recently identified common type 2 diabetes (T2D) susceptibility genetic variants and pancreatic cancer risk. METHODS: Using data on individuals of European ancestry from the Cancer Genetic Markers of Susceptibility PanScan-I study (1,763 pancreatic cancer cases and 1,802 controls), we tested associations for 37 T2D susceptibility variants with pancreatic cancer risk. Associations with pancreatic cancer were also tested for three composite T2D susceptibility measures, incorporating data on all 37 variants, and for ten additional variants related to T2D-related phenotypes, including fasting glucose and beta-cell function. RESULTS: Of the 37 T2D risk alleles, two showed nominally significant positive associations with pancreatic cancer risk (FTO rs8050136 per-allele OR = 1.12; CI: 1.02-1.23; MTNR1B rs1387153 OR = 1.11; CI: 1.00-1.23) and one showed an inverse association (BCL11A rs243021 OR = 0.88; CI: 0.80-0.97). The composite T2D susceptibility measures were not associated with pancreatic cancer. The glucose-raising allele of MADD rs11039149 was associated with increased risk of pancreatic cancer (OR = 1.14; CI: 1.03-1.27). CONCLUSIONS: Overall, these results do not provide strong evidence that common variants underling T2D or related phenotypes also affect pancreatic cancer risk; however, associations for FTO, MTNR1B, BCL11A, and MADD variants warrant further investigation in larger studies. Hypothesis-driven analyses of existing genome-wide genetic data can be cost-efficient and promising approaches for investigating genetic susceptibility to complex diseases.

7 Article Variant ABO blood group alleles, secretor status, and risk of pancreatic cancer: results from the pancreatic cancer cohort consortium. 2010

Wolpin, Brian M / Kraft, Peter / Xu, Mousheng / Steplowski, Emily / Olsson, Martin L / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / LaCroix, Andrea / Petersen, Gloria / Stolzenberg-Solomon, Rachael Z / Zheng, Wei / Albanes, Demetrius / Allen, Naomi E / Amundadottir, Laufey / Austin, Melissa A / Boutron-Ruault, Marie-Christine / Buring, Julie E / Canzian, Federico / Chanock, Stephen J / Gaziano, J Michael / Giovannucci, Edward L / Hallmans, Göran / Hankinson, Susan E / Hoover, Robert N / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Kooperberg, Charles / Mendelsohn, Julie B / Michaud, Dominique S / Overvad, Kim / Patel, Alpa V / Sanchéz, Maria-José / Sansbury, Leah / Shu, Xiao-Ou / Slimani, Nadia / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vineis, Paolo / Visvanathan, Kala / Virtamo, Jarmo / Wactawski-Wende, Jean / Watters, Joanne / Yu, Kai / Zeleniuch-Jacquotte, Anne / Hartge, Patricia / Fuchs, Charles S. ·Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. bwolpin@partners.org ·Cancer Epidemiol Biomarkers Prev · Pubmed #20971884.

ABSTRACT: BACKGROUND: Subjects with non-O ABO blood group alleles have increased risk of pancreatic cancer. Glycosyltransferase activity is greater for the A(1) versus A(2) variant, whereas O01 and O02 variants are nonfunctioning. We hypothesized: 1) A(1) allele would confer greater risk than A(2) allele, 2) protective effect of the O allele would be equivalent for O01 and O02 variants, 3) secretor phenotype would modify the association with risk. METHODS: We determined ABO variants and secretor phenotype from single nucleotide polymorphisms in ABO and FUT2 genes in 1,533 cases and 1,582 controls from 12 prospective cohort studies. Adjusted odds ratios (OR) for pancreatic cancer were calculated using logistic regression. RESULTS: An increased risk was observed in participants with A(1) but not A(2) alleles. Compared with subjects with genotype O/O, genotypes A(2)/O, A(2)/A(1), A(1)/O, and A(1)/A(1) had ORs of 0.96 (95% CI, 0.72-1.26), 1.46 (95% CI, 0.98-2.17), 1.48 (95% CI, 1.23-1.78), and 1.71 (95% CI, 1.18-2.47). Risk was similar for O01 and O02 variant O alleles. Compared with O01/O01, the ORs for each additional allele of O02, A(1), and A(2) were 1.00 (95% CI, 0.87-1.14), 1.38 (95% CI, 1.20-1.58), and 0.96 (95% CI, 0.77-1.20); P, O01 versus O02 = 0.94, A(1) versus A(2) = 0.004. Secretor phenotype was not an effect modifier (P-interaction = 0.63). CONCLUSIONS: Among participants in a large prospective cohort consortium, ABO allele subtypes corresponding to increased glycosyltransferase activity were associated with increased pancreatic cancer risk. IMPACT: These data support the hypothesis that ABO glycosyltransferase activity influences pancreatic cancer risk rather than actions of other nearby genes on chromosome 9q34.

8 Article Association of diabetes susceptibility gene calpain-10 with pancreatic cancer among smokers. 2010

Fong, Pui-yee / Fesinmeyer, Megan D / White, Emily / Farin, Federico M / Srinouanprachanh, Sengkeo / Afsharinejad, Zahra / Mandelson, Margaret T / Brentnall, Teresa A / Barnett, Matt J / Goodman, Gary E / Austin, Melissa A. ·Institute for Public Health Genetics, University of Washington, Box 357236, Seattle, WA 98195, USA. ·J Gastrointest Cancer · Pubmed #20178008.

ABSTRACT: OBJECTIVE: The objective of this study was to test the association between calpain-10 (CAPN10), a diabetes susceptibility gene, with risk of pancreatic cancer (PC). METHODS: DNA samples from 83 incident exocrine PC cases and 166 controls, all of whom were smokers, were genotyped for four markers of CAPN10 in a nested case-control study based on the Beta-Carotene and Retinol Efficacy Trial (CARET), a randomized chemoprevention trial of subjects at high risk of lung cancer. Controls were matched on sex, race, age, CARET intervention arm, duration of exposure to asbestos, and smoking history. Conditional logistic regression was used for statistical analyses. RESULTS: The minor allele of SNP-43 (rs3792267) in intron 3 was associated with increased risk of PC with an odds ratio of 1.57 (95%CI 1.03-2.38, p = 0.035) per allele. The three markers of the highest risk haplotype had an odds ratio of 1.98 (95%CI 1.12-3.49, p = 0.019) for risk of PC compared to the most common haplotype. There was no evidence of interaction between either of these associations by diabetes status. CONCLUSION: These results suggest that variation in CAPN10 may be associated with increased risk of PC among smokers. Thus, studies of genes associated with diabetes risk in PC are warranted in a larger population.

9 Article Association between the peroxisome proliferator-activated receptor gamma Pro12Ala variant and haplotype and pancreatic cancer in a high-risk cohort of smokers: a pilot study. 2009

Fesinmeyer, Megan Dann / Stanford, Janet L / Brentnall, Teresa A / Mandelson, Margaret T / Farin, Federico M / Srinouanprachanh, Sengkeo / Afsharinejad, Zahra / Goodman, Gary E / Barnett, Matt J / Austin, Melissa A. ·Institute for Public Health Genetics, University of Washington, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Department of Epidemiology, Seattle, WA 98195, USA. ·Pancreas · Pubmed #19436234.

ABSTRACT: OBJECTIVES: The Pro12Ala variant in the peroxisome proliferator-activated receptor gamma (PPARG) gene has been associated with diabetes and several cancers. This pilot study tested for the association between Pro12Ala and pancreatic cancer risk in a high-risk sample of smokers. METHODS: A nested case-control study was conducted in 83 incident cases of pancreatic cancer and 166 matched controls originally recruited into a cohort chemoprevention study of lung cancer. Associations between Pro12Ala and pancreatic cancer risk were measured using conditional logistic regression. RESULTS: Carriers of the G allele (Ala) of the Pro12Ala variant had a borderline increased relative risk of pancreatic cancer compared with homozygous carriers of the C allele (Pro), with an odds ratio of 1.79 (95% confidence interval [CI], 0.96-3.33; P=0.06). Among subjects randomized to high-dose vitamin A, the odds ratio was 2.80 (95% CI, 1.16-6.74; P=0.02) versus 1.20 (95% CI, 0.45-3.23; P=0.71) in the placebo group. A haplotype including Pro12Ala was also significantly associated with pancreatic cancer risk in all subjects and in subjects randomized to vitamin A. CONCLUSIONS: This analysis presents the first evidence that PPARG may be associated with pancreatic cancer risk, and this candidate gene should be investigated in future, larger studies.