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Pancreatic Neoplasms: HELP
Articles by Myron D. Gross
Based on 22 articles published since 2009
(Why 22 articles?)
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Between 2009 and 2019, Myron Gross wrote the following 22 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Soluble MICA is elevated in pancreatic cancer: Results from a population based case-control study. 2017

Onyeaghala, Guillaume / Nelson, Heather H / Thyagarajan, Bharat / Linabery, Amy M / Panoskaltsis-Mortari, Angela / Gross, Myron / Anderson, Kristin E / Prizment, Anna E. ·Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota. · University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota. · Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota. · Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. ·Mol Carcinog · Pubmed #28470829.

ABSTRACT: Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates in the United States, creating an urgent need for novel early detection tools. A candidate biomarker for use in early detection is the soluble MHC class I-related chain A (s-MICA) ligand, which pancreatic tumors shed to escape immune detection. The objective of this study was to define the association between s-MICA levels and pancreatic cancer, in a population-based case-control study. S-MICA was measured in 143 pancreatic cancer cases and 459 controls. Unconditional logistic regression was used to calculate odds ratio (OR) for pancreatic cancer and 95% confidence intervals (CI). There was a positive association between increasing s-MICA levels and pancreatic cancer: compared to the lowest tertile, the ORs for pancreatic cancer were 1.25 (95%CI: 0.75-2.07) and 2.10 (95%CI: 1.29-3.42) in the second and highest tertiles, respectively (P-trend = 0.02). Our study supports previous work demonstrating a positive association between plasma s-MICA levels and pancreatic cancer.

2 Article Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. 2016

Zhang, Mingfeng / Wang, Zhaoming / Obazee, Ofure / Jia, Jinping / Childs, Erica J / Hoskins, Jason / Figlioli, Gisella / Mocci, Evelina / Collins, Irene / Chung, Charles C / Hautman, Christopher / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E / Goodman, Phyllis J / Kamineni, Aruna / Kolonel, Laurence N / Kulke, Matthew H / Malats, Núria / Olson, Sara H / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Brais, Lauren / Bueno-de-Mesquita, H Bas / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Bijlsma, Maarten F / Brenner, Hermann / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Cavestro, Giulia Martina / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Boggi, Ugo / Gaziano, J Michael / Gazouli, Maria / Giovannucci, Edward L / Goggins, Michael / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Hu, Nan / Hunter, David J / Iskierka-Jazdzewska, Elzbieta / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Neale, Rachel E / Oberg, Ann L / Panico, Salvatore / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Purdue, Mark / Quiros, J Ramón / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Scelo, Ghislaine / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Strobel, Oliver / Sund, Malin / Małecka-Panas, Ewa / Taylor, Philip R / Tavano, Francesca / Travis, Ruth C / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vashist, Yogesh / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Kooperberg, Charles / Risch, Harvey A / Jacobs, Eric J / Li, Donghui / Fuchs, Charles / Hoover, Robert / Hartge, Patricia / Chanock, Stephen J / Petersen, Gloria M / Stolzenberg-Solomon, Rachael S / Wolpin, Brian M / Kraft, Peter / Klein, Alison P / Canzian, Federico / Amundadottir, Laufey T. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · 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. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. · Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. · New York University Cancer Institute, New York, New York, USA,. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. · Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia. · 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. · Group Health Research Institute, Seattle, Washington, USA,. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, 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 Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy,. · Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F-94805, Villejuif, France. · University Paris Sud, UMRS 1018, F-94805, Villejuif, France. · IGR, F-94805, Villejuif, France. · Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Biology, University of Pisa, Pisa, Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada. · 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, United Kingdom. · 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. · Massachusetts Veteran's Epidemiology, Research, and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. · Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · 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. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. · Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Harvard School of Public Health, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · Department of Hematology, Medical University of Łodz, Łodz, Poland. · International Agency for Research on Cancer (IARC), Lyon, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. · School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA. · Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Spain. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. · 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. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland. · Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Dipartimento di Medicina Clinica E Chirurgia, Federico II Univeristy, Naples, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Public Health and Participation Directorate, Asturias, Spain. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Surgical and Peroperative Sciences, Umeå University, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. · Hellenic Health Foundation, Athens, Greece. · Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, Hamburg, Germany. · 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, Buffalo, New York, USA. · New York University Cancer Institute, New York, New York, USA. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA,. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland, USA. ·Oncotarget · Pubmed #27579533.

ABSTRACT: 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 = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -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 = 5.7x10 -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 = 7.5x10 -4-2.0x10 -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.

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

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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 Genome-wide association study of survival in patients with pancreatic adenocarcinoma. 2014

Wu, Chen / Kraft, Peter / Stolzenberg-Solomon, Rachael / Steplowski, Emily / Brotzman, Michelle / Xu, Mousheng / Mudgal, Poorva / Amundadottir, Laufey / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / Kooperberg, Charles / Petersen, Gloria M / Zheng, Wei / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Buring, Julie E / Canzian, Federico / Cao, Guangwen / Duell, Eric J / Elena, Joanne W / Gaziano, J Michael / Giovannucci, Edward L / Hallmans, Goran / Hutchinson, Amy / Hunter, David J / Jenab, Mazda / Jiang, Guoliang / Khaw, Kay-Tee / LaCroix, Andrea / Li, Zhaoshen / Mendelsohn, Julie B / Panico, Salvatore / Patel, Alpa V / Qian, Zhi Rong / Riboli, Elio / Sesso, Howard / Shen, Hongbing / Shu, Xiao-Ou / Tjonneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Wactawski-Wende, Jean / Wang, Chengfeng / Yu, Kai / Zeleniuch-Jacquotte, Anne / Chanock, Stephen / Hoover, Robert / Hartge, Patricia / Fuchs, Charles S / Lin, Dongxin / Wolpin, Brian M. ·Department of Epidemiology, Harvard School of Public Health, , Boston, Massachusetts, USA. ·Gut · Pubmed #23180869.

ABSTRACT: BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

6 Article An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population. 2013

Klein, Alison P / Lindström, Sara / Mendelsohn, Julie B / Steplowski, Emily / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Fuchs, Charles S / Gallinger, Steven / Gross, Myron / Helzlsouer, Kathy / Holly, Elizabeth A / Jacobs, Eric J / Lacroix, Andrea / Li, Donghui / Mandelson, Margaret T / Olson, Sara H / Petersen, Gloria M / Risch, Harvey A / Stolzenberg-Solomon, Rachael Z / Zheng, Wei / Amundadottir, Laufey / Albanes, Demetrius / Allen, Naomi E / Bamlet, William R / Boutron-Ruault, Marie-Christine / Buring, Julie E / Bracci, Paige M / Canzian, Federico / Clipp, Sandra / Cotterchio, Michelle / Duell, Eric J / Elena, Joanne / Gaziano, J Michael / Giovannucci, Edward L / Goggins, Michael / Hallmans, Göran / Hassan, Manal / Hutchinson, Amy / Hunter, David J / Kooperberg, Charles / Kurtz, Robert C / Liu, Simin / Overvad, Kim / Palli, Domenico / Patel, Alpa V / Rabe, Kari G / Shu, Xiao-Ou / Slimani, Nadia / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Van Den Eeden, Stephen K / Vineis, Paolo / Virtamo, Jarmo / Wactawski-Wende, Jean / Wolpin, Brian M / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Chanock, Stephen J / Hoover, Robert N / Hartge, Patricia / Kraft, Peter. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States of America ; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. ·PLoS One · Pubmed #24058443.

ABSTRACT: PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

7 Article Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4. 2013

Leenders, Max / Bhattacharjee, Samsiddhi / Vineis, Paolo / Stevens, Victoria / Bueno-de-Mesquita, H Bas / Shu, Xiao-Ou / Amundadottir, Laufey / Gross, Myron / Tobias, Geoffrey S / Wactawski-Wende, Jean / Arslan, Alan A / Duell, Eric J / Fuchs, Charles S / Gallinger, Steven / Hartge, Patricia / Hoover, Robert N / Holly, Elizabeth A / Jacobs, Eric J / Klein, Alison P / Kooperberg, Charles / LaCroix, Andrea / Li, Donghui / Mandelson, Margaret T / Olson, Sara H / Petersen, Gloria / Risch, Harvey A / Yu, Kai / Wolpin, Brian M / Zheng, Wei / Agalliu, Ilir / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Buring, Julie E / Canzian, Federico / Chang, Kenneth / Chanock, Stephen J / Cotterchio, Michelle / Gaziano, J Michael / Giovanucci, Edward L / Goggins, Michael / Hallmans, Göran / Hankinson, Susan E / Hoffman-Bolton, Judith A / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Jenab, Mazda / Khaw, Kay-Tee / Kraft, Peter / Krogh, Vittorio / Kurtz, Robert C / McWilliams, Robert R / Mendelsohn, Julie B / Patel, Alpa V / Rabe, Kari G / Riboli, Elio / Tjønneland, Anne / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Elena, Joanne W / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Stolzenberg-Solomon, Rachael Z. ·Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. M.Leenders-6@umcutrecht.nl ·Cancer Causes Control · Pubmed #23334854.

ABSTRACT: PURPOSE: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. METHODS: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. RESULTS: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. CONCLUSIONS: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

8 Article Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. 2013

Elena, Joanne W / Steplowski, Emily / Yu, Kai / Hartge, Patricia / Tobias, Geoffrey S / Brotzman, Michelle J / Chanock, Stephen J / Stolzenberg-Solomon, Rachael Z / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Helzlsouer, Kathy / Jacobs, Eric J / LaCroix, Andrea / Petersen, Gloria / Zheng, Wei / Albanes, Demetrius / Allen, Naomi E / Amundadottir, Laufey / Bao, Ying / Boeing, Heiner / Boutron-Ruault, Marie-Christine / Buring, Julie E / Gaziano, J Michael / Giovannucci, Edward L / Duell, Eric J / Hallmans, Göran / Howard, Barbara V / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Kooperberg, Charles / Kraft, Peter / Mendelsohn, Julie B / Michaud, Dominique S / Palli, Domenico / Phillips, Lawrence S / Overvad, Kim / Patel, Alpa V / Sansbury, Leah / Shu, Xiao-Ou / Simon, Michael S / Slimani, Nadia / Trichopoulos, Dimitrios / Visvanathan, Kala / Virtamo, Jarmo / Wolpin, Brian M / Zeleniuch-Jacquotte, Anne / Fuchs, Charles S / Hoover, Robert N / Gross, Myron. ·Division of Cancer Control and Population Science, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. elenajw@mail.nih.gov ·Cancer Causes Control · Pubmed #23112111.

ABSTRACT: PURPOSE: Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). METHODS: The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. RESULTS: Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). CONCLUSIONS: These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.

9 Article Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer. 2012

Li, Donghui / Duell, Eric J / Yu, Kai / Risch, Harvey A / Olson, Sara H / Kooperberg, Charles / Wolpin, Brian M / Jiao, Li / Dong, Xiaoqun / Wheeler, Bill / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Fuchs, Charles S / Gallinger, Steven / Gross, Myron / Hartge, Patricia / Hoover, Robert N / Holly, Elizabeth A / Jacobs, Eric J / Klein, Alison P / LaCroix, Andrea / Mandelson, Margaret T / Petersen, Gloria / Zheng, Wei / Agalliu, Ilir / Albanes, Demetrius / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Buring, Julie E / Canzian, Federico / Chang, Kenneth / Chanock, Stephen J / Cotterchio, Michelle / Gaziano, J Michael / Giovannucci, Edward L / Goggins, Michael / Hallmans, Göran / Hankinson, Susan E / Hoffman Bolton, Judith A / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Jenab, Mazda / Khaw, Kay-Tee / Kraft, Peter / Krogh, Vittorio / Kurtz, Robert C / McWilliams, Robert R / Mendelsohn, Julie B / Patel, Alpa V / Rabe, Kari G / Riboli, Elio / Shu, Xiao-Ou / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Visvanathan, Kala / Watters, Joanne / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Amundadottir, Laufey / Stolzenberg-Solomon, Rachael Z. ·Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. ·Carcinogenesis · Pubmed #22523087.

ABSTRACT: Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10(-6), 1.6 × 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10(-5)), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer.

10 Article Pancreatic cancer risk: associations with meat-derived carcinogen intake in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. 2012

Anderson, Kristin E / Mongin, Steven J / Sinha, Rashmi / Stolzenberg-Solomon, Rachael / Gross, Myron D / Ziegler, Regina G / Mabie, Jerome E / Risch, Adam / Kazin, Sally S / Church, Timothy R. ·Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota 55454, USA. ·Mol Carcinog · Pubmed #22162237.

ABSTRACT: BACKGROUND: Epidemiological studies report positive associations between high-temperature cooked meat intake and pancreatic cancer. We assessed associations between dietary intake of heterocyclic amines (HCAs) and benzo(a)pyrene (BaP)-mutagens formed in meat cooked at high temperatures-and incident exocrine pancreatic cancer in a prospective cohort. METHODS: The 62 581 subjects randomized to screening in the Prostate, Lung, Colorectal, and Ovarian Screening Trial (PLCO) who completed an initial dietary survey that assessed meat intake, cooking methods, and doneness preferences defined the cohort. Subjects were surveyed annually for incident cancers through 2007. A National Cancer Institute research database (CHARRED) was used to estimate HCA and BaP intake and a Mutagenic Activity Index (MAI) from survey data. Proportional hazard ratios (HRs) for risk of pancreatic cancer were estimated from multi-variate Cox regression models by quintile of intake, with the lowest quintile as the referent. RESULTS: During follow-up (median: 10 yr), 248 cases of exocrine pancreatic cancer were confirmed. Preferences for well and very well done meat were generally associated with increased risks. Significant elevations in pancreatic cancer risk were found in upper quintiles of MAI, and individual mutagens 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Compared to the lowest quintile of MAI, the third and fifth quintiles brought HRs of 1.86 (1.22, 2.85) and 1.87 (1.16, 3.02), respectively. These three exposures exhibited significant (P-trend: 0.01-0.03) positive trends in risk as their levels increased CONCLUSION: Consuming well-done meat cooked at high temperatures, which contains high mutagen levels, appears to confer increased risk of pancreatic cancer.

11 Article Genes related to diabetes may be associated with pancreatic cancer in a population-based case-control study in Minnesota. 2012

Prizment, Anna E / Gross, Myron / Rasmussen-Torvik, Laura / Peacock, James M / Anderson, Kristin E. ·Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA. prizm001@umn.edu ·Pancreas · Pubmed #22015968.

ABSTRACT: OBJECTIVES: Type 2 diabetes is associated with increased pancreatic cancer risk; however, the nature of this relationship is not clear. We examined the link between 10 diabetes-related single-nucleotide polymorphisms and pancreatic cancer in a case-control study conducted in 1994 to 1998. METHODS: Cases (n = 162) were ascertained from hospitals in the Twin Cities and Mayo Clinic, Minn. Controls (n = 540) from the general population were frequency matched by age, sex, and race. Unconditional logistic regression provided odds ratios of pancreatic cancer and 95% confidence intervals (95% CIs). RESULTS: In a multivariate-adjusted model, a significant association was observed only for rs780094 in the glucokinase regulator (GCKR) gene: odds ratios for pancreatic cancer were 1.00 for TT, 1.35 (95% CI, 0.71-2.58) for CT, and 2.14 (95% CI, 1.12-4.08) for CC genotypes (P trend = 0.01) and did not change after the adjustment for diabetes. CONCLUSIONS: This study provides the first evidence that GCKR rs780094, a single-nucleotide polymorphism related to diabetes, may be associated with pancreatic cancer risk. Although the results from this analysis are preliminary, there is a biologic plausibility for such an association.

12 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.

13 Article Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). 2010

Arslan, Alan A / Helzlsouer, Kathy J / Kooperberg, Charles / Shu, Xiao-Ou / Steplowski, Emily / Bueno-de-Mesquita, H Bas / Fuchs, Charles S / Gross, Myron D / Jacobs, Eric J / Lacroix, Andrea Z / Petersen, Gloria M / Stolzenberg-Solomon, Rachael Z / Zheng, Wei / Albanes, Demetrius / Amundadottir, Laufey / Bamlet, William R / Barricarte, Aurelio / Bingham, Sheila A / Boeing, Heiner / Boutron-Ruault, Marie-Christine / Buring, Julie E / Chanock, Stephen J / Clipp, Sandra / Gaziano, J Michael / Giovannucci, Edward L / Hankinson, Susan E / Hartge, Patricia / Hoover, Robert N / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin B / Kraft, Peter / Lynch, Shannon M / Manjer, Jonas / Manson, Joann E / McTiernan, Anne / McWilliams, Robert R / Mendelsohn, Julie B / Michaud, Dominique S / Palli, Domenico / Rohan, Thomas E / Slimani, Nadia / Thomas, Gilles / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Wolpin, Brian M / Yu, Kai / Zeleniuch-Jacquotte, Anne / Patel, Alpa V / Anonymous4971513. ·Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Ave, TH-528, New York, NY 10016, USA. alan.arslan@nyumc.org ·Arch Intern Med · Pubmed #20458087.

ABSTRACT: BACKGROUND: Obesity has been proposed as a risk factor for pancreatic cancer. METHODS: Pooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight, height, waist circumference, and waist to hip ratio as well as conventional BMI categories (underweight, <18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese, 30.0-34.9; and severely obese, > or = 35.0). Models were adjusted for potential confounders. RESULTS: In all of the participants, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs lowest BMI quartile, 1.33; 95% CI, 1.12-1.58; P(trend) < .001). In men, the adjusted OR for pancreatic cancer for the highest vs lowest quartile of BMI was 1.33 (95% CI, 1.04-1.69; P(trend) < .03), and in women it was 1.34 (95% CI, 1.05-1.70; P(trend) = .01). Increased waist to hip ratio was associated with increased risk of pancreatic cancer in women (adjusted OR for the highest vs lowest quartile, 1.87; 95% CI, 1.31-2.69; P(trend) = .003) but less so in men. CONCLUSIONS: These findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women.

14 Article Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan). 2010

Michaud, Dominique S / Vrieling, Alina / Jiao, Li / Mendelsohn, Julie B / Steplowski, Emily / Lynch, Shannon M / Wactawski-Wende, Jean / Arslan, Alan A / Bas Bueno-de-Mesquita, H / Fuchs, Charles S / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / Lacroix, Andrea / Petersen, Gloria / Zheng, Wei / Allen, Naomi / Ammundadottir, Laufey / Bergmann, Manuela M / Boffetta, Paolo / Buring, Julie E / Canzian, Federico / Chanock, Stephen J / Clavel-Chapelon, Françoise / Clipp, Sandra / Freiberg, Matthew S / Michael Gaziano, J / Giovannucci, Edward L / Hankinson, Susan / Hartge, Patricia / Hoover, Robert N / Allan Hubbell, F / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin / Kooperberg, Charles / Kraft, Peter / Manjer, Jonas / Navarro, Carmen / Peeters, Petra H M / Shu, Xiao-Ou / Stevens, Victoria / Thomas, Gilles / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Tumino, Rosario / Vineis, Paolo / Virtamo, Jarmo / Wallace, Robert / Wolpin, Brian M / Yu, Kai / Zeleniuch-Jacquotte, Anne / Stolzenberg-Solomon, Rachael Z. ·Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK. d.michaud@imperial.ac.uk ·Cancer Causes Control · Pubmed #20373013.

ABSTRACT: The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. >0 to <5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out.

15 Article Soft drink and juice consumption and risk of pancreatic cancer: the Singapore Chinese Health Study. 2010

Mueller, Noel T / Odegaard, Andrew / Anderson, Kristin / Yuan, Jian-Min / Gross, Myron / Koh, Woon-Puay / Pereira, Mark A. ·Cancer Control Program, Georgetown University Medical Center, Washington, District of Columbia, USA. ·Cancer Epidemiol Biomarkers Prev · Pubmed #20142243.

ABSTRACT: BACKGROUND: Sugar-sweetened carbonated beverages (called soft drinks) and juices, which have a high glycemic load relative to other foods and beverages, have been hypothesized as pancreatic cancer risk factors. However, data thus far are scarce, especially from non-European descent populations. We investigated whether higher consumption of soft drinks and juice increases the risk of pancreatic cancer in Chinese men and women. METHODS: A prospective cohort analysis was done to examine the association between soft drink and juice consumption and the risk of pancreatic cancer in 60,524 participants of the Singapore Chinese Health Study with up to 14 years of follow-up. Information on consumption of soft drinks, juice, and other dietary items, as well as lifestyle and environmental exposures, was collected through in-person interviews at recruitment. Pancreatic cancer cases and deaths were ascertained by record linkage of the cohort database with records of population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths. RESULTS: The first 14 years for the cohort resulted in cumulative 648,387 person-years and 140 incident pancreatic cancer cases. Individuals consuming > or = 2 soft drinks/wk experienced a statistically significant increased risk of pancreatic cancer (hazard ratio, 1.87; 95% confidence interval, 1.10-3.15) compared with individuals who did not consume soft drinks after adjustment for potential confounders. There was no statistically significant association between juice consumption and risk of pancreatic cancer. CONCLUSION: Regular consumption of soft drinks may play an independent role in the development of pancreatic cancer.

16 Article Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium. 2010

Wolpin, Brian M / Kraft, Peter / Gross, Myron / Helzlsouer, Kathy / Bueno-de-Mesquita, H Bas / Steplowski, Emily / Stolzenberg-Solomon, Rachael Z / Arslan, Alan A / Jacobs, Eric J / Lacroix, Andrea / Petersen, Gloria / Zheng, Wei / Albanes, Demetrius / Allen, Naomi E / Amundadottir, Laufey / Anderson, Garnet / Boutron-Ruault, Marie-Christine / Buring, Julie E / Canzian, Federico / Chanock, Stephen J / Clipp, Sandra / Gaziano, John Michael / Giovannucci, Edward L / Hallmans, Göran / Hankinson, Susan E / Hoover, Robert N / Hunter, David J / Hutchinson, Amy / Jacobs, Kevin / Kooperberg, Charles / Lynch, Shannon M / Mendelsohn, Julie B / Michaud, Dominique S / Overvad, Kim / Patel, Alpa V / Rajkovic, Aleksandar / Sanchéz, Maria-José / Shu, Xiao-Ou / Slimani, Nadia / Thomas, Gilles / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vineis, Paolo / Virtamo, Jarmo / Wactawski-Wende, Jean / 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 Res · Pubmed #20103627.

ABSTRACT: A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk.

17 Article A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. 2010

Petersen, Gloria M / Amundadottir, Laufey / Fuchs, Charles S / Kraft, Peter / Stolzenberg-Solomon, Rachael Z / Jacobs, Kevin B / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gallinger, Steven / Gross, Myron / Helzlsouer, Kathy / Holly, Elizabeth A / Jacobs, Eric J / Klein, Alison P / LaCroix, Andrea / Li, Donghui / Mandelson, Margaret T / Olson, Sara H / Risch, Harvey A / Zheng, Wei / Albanes, Demetrius / Bamlet, William R / Berg, Christine D / Boutron-Ruault, Marie-Christine / Buring, Julie E / Bracci, Paige M / Canzian, Federico / Clipp, Sandra / Cotterchio, Michelle / de Andrade, Mariza / Duell, Eric J / Gaziano, J Michael / Giovannucci, Edward L / Goggins, Michael / Hallmans, Göran / Hankinson, Susan E / Hassan, Manal / Howard, Barbara / Hunter, David J / Hutchinson, Amy / Jenab, Mazda / Kaaks, Rudolf / Kooperberg, Charles / Krogh, Vittorio / Kurtz, Robert C / Lynch, Shannon M / McWilliams, Robert R / Mendelsohn, Julie B / Michaud, Dominique S / Parikh, Hemang / Patel, Alpa V / Peeters, Petra H M / Rajkovic, Aleksandar / Riboli, Elio / Rodriguez, Laudina / Seminara, Daniela / Shu, Xiao-Ou / Thomas, Gilles / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Van Den Eeden, Stephen K / Virtamo, Jarmo / Wactawski-Wende, Jean / Wang, Zhaoming / Wolpin, Brian M / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Fraumeni, Joseph F / Hoover, Robert N / Hartge, Patricia / Chanock, Stephen J. ·Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA. ·Nat Genet · Pubmed #20101243.

ABSTRACT: We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

18 Article Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). 2010

Jacobs, Eric J / Chanock, Stephen J / Fuchs, Charles S / Lacroix, Andrea / McWilliams, Robert R / Steplowski, Emily / Stolzenberg-Solomon, Rachael Z / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gross, Myron / Helzlsouer, Kathy / Petersen, Gloria / Zheng, Wei / Agalliu, Ilir / Allen, Naomi E / Amundadottir, Laufey / Boutron-Ruault, Marie-Christine / Buring, Julie E / Canzian, Federico / Clipp, Sandra / Dorronsoro, Miren / Gaziano, J Michael / Giovannucci, Edward L / Hankinson, Susan E / Hartge, Patricia / Hoover, Robert N / Hunter, David J / Jacobs, Kevin B / Jenab, Mazda / Kraft, Peter / Kooperberg, Charles / Lynch, Shannon M / Sund, Malin / Mendelsohn, Julie B / Mouw, Tracy / Newton, Christina C / Overvad, Kim / Palli, Domenico / Peeters, Petra H M / Rajkovic, Aleksandar / Shu, Xiao-Ou / Thomas, Gilles / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Virtamo, Jarmo / Wactawski-Wende, Jean / Wolpin, Brian M / Yu, Kai / Zeleniuch-Jacquotte, Anne. ·Department of Epidemiology, American Cancer Society, Atlanta, GA, USA. ejacobs@cancer.org ·Int J Cancer · Pubmed #20049842.

ABSTRACT: A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.

19 Article Physical activity, diet, and pancreatic cancer: a population-based, case-control study in Minnesota. 2009

Zhang, Jianjun / Dhakal, Ishwori B / Gross, Myron D / Lang, Nicholas P / Kadlubar, Fred F / Harnack, Lisa J / Anderson, Kristin E. ·University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. zhangjianjun@uams.edu ·Nutr Cancer · Pubmed #19838917.

ABSTRACT: Although mounting evidence suggests that insulin resistance is involved in pancreatic carcinogenesis, few epidemiologic studies have comprehensively investigated the role of lifestyle factors influencing this metabolic disorder in the etiology of pancreatic cancer. We sought to examine this problem in a case-control study conducted in 1994-1998 in Minnesota. Cases (n = 186), aged 20 yr or older, were ascertained from all hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic; from the latter, only cases residing in the Upper Midwest of the United States were recruited. Controls (n = 554) were randomly selected from the general population and frequency matched to cases by age (within 5 yr) and sex. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. After adjustment for confounders, physical activity was associated with a reduced risk, but this protective effect was confined to light activity and moderate activity only (OR = 0.55, 95% CI = 0.30-0.97, P(trend) = 0.038 and OR = 0.51, 95% CI = 0.28-0.93, P(trend) = 0.07, for highest vs. lowest quartile, respectively). An increased risk was found for dietary intakes of energy and fat but was statistically significant for saturated and polyunsaturated fat only. Of note, no appreciable difference in the magnitude of the associations existed between saturated, monounsaturated, and polyunsaturated fat. Compared with individuals in the lowest quartile of fiber intake, the risk was approximately halved for those in the third (OR = 0.49, 95% CI = 0.26-0.94) and the highest quartile (OR = 0.52, 95% CI = 0.21-1.30). Our study lends support to the hypothesis that dietary and other lifestyle factors influencing insulin resistance modulate pancreatic cancer risk.

20 Article Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. 2009

Lynch, Shannon M / Vrieling, Alina / Lubin, Jay H / Kraft, Peter / Mendelsohn, Julie B / Hartge, Patricia / Canzian, Federico / Steplowski, Emily / Arslan, Alan A / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / LaCroix, Andrea / Petersen, Gloria / Zheng, Wei / Albanes, Demetrius / Amundadottir, Laufey / Bingham, Sheila A / Boffetta, Paolo / Boutron-Ruault, Marie-Christine / Chanock, Stephen J / Clipp, Sandra / Hoover, Robert N / Jacobs, Kevin / Johnson, Karen C / Kooperberg, Charles / Luo, Juhua / Messina, Catherine / Palli, Domenico / Patel, Alpa V / Riboli, Elio / Shu, Xiao-Ou / Rodriguez Suarez, Laudina / Thomas, Gilles / Tjønneland, Anne / Tobias, Geoffrey S / Tong, Elissa / Trichopoulos, Dimitrios / Virtamo, Jarmo / Ye, Weimin / Yu, Kai / Zeleniuch-Jacquette, Anne / Bueno-de-Mesquita, H Bas / Stolzenberg-Solomon, Rachael Z. ·National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA. lynchs@mail.nih.gov ·Am J Epidemiol · Pubmed #19561064.

ABSTRACT: Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (> or =30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (> or =50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (> or =40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.

21 Article Phenotypic CYP2A6 variation and the risk of pancreatic cancer. 2009

Kadlubar, Susan / Anderson, Jeffrey P / Sweeney, Carol / Gross, Myron D / Lang, Nicholas P / Kadlubar, Fred F / Anderson, Kristin E. ·Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. sakadlubar@uams.edu ·JOP · Pubmed #19454817.

ABSTRACT: OBJECTIVE: Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme capable of activating several procarcinogens, including dietary and tobacco-specific nitrosamines, which have been linked to pancreatic cancer. Positive associations between high CYP2A6 activity and lung and colorectal cancers have been reported. This is the first investigation of CYP2A6 activity and pancreatic cancer. DESIGN: In this case-control study of cancer of the exocrine pancreas, phenotypic CYP2A6 activity was measured using a ratio of urinary caffeine metabolites. Demographic, smoking, dietary and medical information were obtained by questionnaire. CYP2A6 phenotype, which is not influenced by smoking status, was measured for 90 cases and 470 controls. RESULTS: When modeled as a continuous variable, and adjusted for age, sex, race, education, current smoking status and chronic pancreatitis, the odds ratio (OR) per one unit of the natural log of the CYP2A6 ratio was 1.52 (95% confidence interval, CI: 1.09-2.12). In an adjusted categorical analysis, subjects in the uppermost quartile (based on controls) of CYP2A6 activity, when compared to the lower three quartiles, carried an 80% greater risk of pancreatic cancer (OR=1.80; 95% CI: 1.07-3.02). CONCLUSIONS: High levels of CYP2A6 activity, as measured by a caffeine phenotyping assay, were positively associated with pancreatic cancer in this casecontrol study among a Midwestern U.S. population.

22 Minor Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. 2009

Amundadottir, Laufey / Kraft, Peter / Stolzenberg-Solomon, Rachael Z / Fuchs, Charles S / Petersen, Gloria M / Arslan, Alan A / Bueno-de-Mesquita, H Bas / Gross, Myron / Helzlsouer, Kathy / Jacobs, Eric J / LaCroix, Andrea / Zheng, Wei / Albanes, Demetrius / Bamlet, William / Berg, Christine D / Berrino, Franco / Bingham, Sheila / Buring, Julie E / Bracci, Paige M / Canzian, Federico / Clavel-Chapelon, Françoise / Clipp, Sandra / Cotterchio, Michelle / de Andrade, Mariza / Duell, Eric J / Fox, John W / Gallinger, Steven / Gaziano, J Michael / Giovannucci, Edward L / Goggins, Michael / González, Carlos A / Hallmans, Göran / Hankinson, Susan E / Hassan, Manal / Holly, Elizabeth A / Hunter, David J / Hutchinson, Amy / Jackson, Rebecca / Jacobs, Kevin B / Jenab, Mazda / Kaaks, Rudolf / Klein, Alison P / Kooperberg, Charles / Kurtz, Robert C / Li, Donghui / Lynch, Shannon M / Mandelson, Margaret / McWilliams, Robert R / Mendelsohn, Julie B / Michaud, Dominique S / Olson, Sara H / Overvad, Kim / Patel, Alpa V / Peeters, Petra H M / Rajkovic, Aleksandar / Riboli, Elio / Risch, Harvey A / Shu, Xiao-Ou / Thomas, Gilles / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Van Den Eeden, Stephen K / Virtamo, Jarmo / Wactawski-Wende, Jean / Wolpin, Brian M / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Chanock, Stephen J / Hartge, Patricia / Hoover, Robert N. · ·Nat Genet · Pubmed #19648918.

ABSTRACT: We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.