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Pancreatic Neoplasms: HELP
Articles by Dimitrios Trichopoulos
Based on 23 articles published since 2010
(Why 23 articles?)
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Between 2010 and 2020, D. Trichopoulos wrote the following 23 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 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.

2 Article Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study. 2014

Campa, Daniele / Mergarten, Björn / De Vivo, Immaculata / Boutron-Ruault, Marie-Christine / Racine, Antoine / Severi, Gianluca / Nieters, Alexandra / Katzke, Verena A / Trichopoulou, Antonia / Yiannakouris, Nikos / Trichopoulos, Dimitrios / Boeing, Heiner / Quirós, J Ramón / Duell, Eric J / Molina-Montes, Esther / Huerta, José María / Ardanaz, Eva / Dorronsoro, Miren / Khaw, Kay-Tee / Wareham, Nicholas / Travis, Ruth C / Palli, Domenico / Pala, Valeria / Tumino, Rosario / Naccarati, Alessio / Panico, Salvatore / Vineis, Paolo / Riboli, Elio / Siddiq, Afshan / Bueno-de-Mesquita, H B / Peeters, Petra H / Nilsson, Peter M / Sund, Malin / Ye, Weimin / Lund, Eiliv / Jareid, Mie / Weiderpass, Elisabete / Duarte-Salles, Talita / Kong, So Yeon / Stepien, Magdalena / Canzian, Federico / Kaaks, Rudolf. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts. · Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones, and Women's Health team, Villejuif, France. Univ Paris Sud, UMRS 1018, Villejuif, France. IGR, Villejuif, France. · Human Genetics Foundation (HuGeF), Torino, Italy. · Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany. · Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. · Hellenic Health Foundation, Athens, Greece. Harokopio University of Athens, Greece. · Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. · Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. · Public Health Directorate, Asturias, Spain. · Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. · Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. · CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. · CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. Navarre Public Health Institute, Pamplona, Spain. · Public Health Direction and Biodonostia-Ciberesp Basque Regional Health Department, San Sebastian, Spain. · University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom. · Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. · Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence, Italy. · Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy. · Dipartimento Di Medicina Clinica e Chirurgia Federico II University, Naples, Italy. · Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom. · Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom. · National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. The School of Public Health, Imperial College London, London, United Kingdom. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands. · Lund University, Department of Clinical Sciences, Skåne University Hospital, Malmö Sweden. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. The Medical Biobank at Umeå University, Umeå, Sweden. · Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. · Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. · International Agency for Research on Cancer (IARC-WHO), Lyon, France. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. r.kaaks@dkfz.de. ·Cancer Epidemiol Biomarkers Prev · Pubmed #25103821.

ABSTRACT: BACKGROUND: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. METHODS: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). RESULTS: We observed that the mean LTL was higher in cases (0.59 ± 0.20) than in controls (0.57 ± 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL. CONCLUSION: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. IMPACT: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and 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 Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. 2014

Bosetti, C / Rosato, V / Li, D / Silverman, D / Petersen, G M / Bracci, P M / Neale, R E / Muscat, J / Anderson, K / Gallinger, S / Olson, S H / Miller, A B / Bas Bueno-de-Mesquita, H / Scelo, G / Janout, V / Holcatova, I / Lagiou, P / Serraino, D / Lucenteforte, E / Fabianova, E / Ghadirian, P / Baghurst, P A / Zatonski, W / Foretova, L / Fontham, E / Bamlet, W R / Holly, E A / Negri, E / Hassan, M / Prizment, A / Cotterchio, M / Cleary, S / Kurtz, R C / Maisonneuve, P / Trichopoulos, D / Polesel, J / Duell, E J / Boffetta, P / La Vecchia, C. ·Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy cristina.bosetti@marionegri.it. · Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy. · M.D. Anderson Cancer Center, University of Texas, Houston. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda. · Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA. · Queensland Institute of Medical Research, Brisbane, Australia. · Department of Public Health Sciences, Penn State University, Penn State. · Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA. · University Health Network, Department of Surgery, University of Toronto, Toronto, Canada. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA. · Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. · National Institute for Public Health and the Environment (RIVM), Bilthoven Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · International Agency for Research on Cancer (IARC), Lyon, France. · Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc. · Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Epidemiology, Harvard School of Public Health, Boston, USA Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece. · Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano. · Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, Università degli Studi di Firenze, Florence, Italy. · Regional Authority of Public Health in Banská Bystrica, Banská Bystrica, Slovakia. · Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy M.D. Anderson Cancer Center, University of Texas, Houston Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA Queensland Institute of Medical Research, Brisbane, Australia Department of Public Health Sciences, Penn State University, Penn State Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA University Health Network, Department of Surgery, University of Toronto, Toronto, Canada Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA Dalla Lana School of Public Health, University of Toronto, Toronto, Canada National Institute for Public Health and the Environment (RIVM), Bilthoven Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK International Agency for Research on Cancer (IARC), Lyon, France Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Department of Epidemiology, Harvard School of Public Health, Boston, USA Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, Università degli Studi di Firenze, Florence, Italy Regional Authority of Public Health in Banská Bystrica, Banská Bystrica, Slovakia Public Health, Women · Public Health, Women's and Children's Hospital, Adelaide, SA, Australia. · Cancer Center and Institute of Oncology, Warsaw, Poland. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic. · Louisiana State University School of Public Health, New Orleans, USA. · Dalla Lana School of Public Health, University of Toronto, Toronto, Canada Cancer Care Ontario, Toronto, Canada. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Department of Epidemiology, Harvard School of Public Health, Boston, USA. · Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. · The Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, USA. · Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. ·Ann Oncol · Pubmed #25057164.

ABSTRACT: BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

5 Article Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data. 2014

Tang, Hongwei / Wei, Peng / Duell, Eric J / Risch, Harvey A / Olson, Sara H / Bueno-de-Mesquita, H Bas / Gallinger, Steven / Holly, Elizabeth A / Petersen, Gloria / Bracci, Paige M / McWilliams, Robert R / Jenab, Mazda / Riboli, Elio / Tjønneland, Anne / Boutron-Ruault, Marie Christine / Kaaks, Rudolph / Trichopoulos, Dimitrios / Panico, Salvatore / Sund, Malin / Peeters, Petra H M / Khaw, Kay-Tee / Amos, Christopher I / Li, Donghui. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·Carcinogenesis · Pubmed #24419231.

ABSTRACT: Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene-smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling $$\left(P=2.12\times 1{0}^{-7}\right)$$ and α-adrenergic signaling $$\left(P=2.52\times 1{0}^{-5}\right)$$ genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer.

6 Article Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis. 2014

Tang, Hongwei / Wei, Peng / Duell, Eric J / Risch, Harvey A / Olson, Sara H / Bueno-de-Mesquita, H Bas / Gallinger, Steven / Holly, Elizabeth A / Petersen, Gloria M / Bracci, Paige M / McWilliams, Robert R / Jenab, Mazda / Riboli, Elio / Tjønneland, Anne / Boutron-Ruault, Marie Christine / Kaaks, Rudolf / Trichopoulos, Dimitrios / Panico, Salvatore / Sund, Malin / Peeters, Petra H M / Khaw, Kay-Tee / Amos, Christopher I / Li, Donghui. ·Authors' Affiliations: Departments of Gastrointestinal Medical Oncology and Epidemiology, The University of Texas MD Anderson Cancer Center; Division of Biostatistics and Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas; Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Yale University School of Public Health, New Haven, Connecticut; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; National Institute for Public Health and the Environment (RIVM), Bilthoven and Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Samuel Lunenfeld Research Institute, Toronto General Hospital, University of Toronto, Toronto, Canada; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; International Agency for Research on Cancer, Lyon; Institut national de la santé et de la recherche medicale (INSERM), Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team; Univ. Paris Sud, UMRS 1018; IGR, F-94805, Villejuif, France; Division of Epidemiology, Public Health, and Primary Care, Imperial College London, London; School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Bureau of Epidemiologic Research, Academy of Athens; Hellenic Health Foundation, Athens, Greece; Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy; and Department ·Cancer Epidemiol Biomarkers Prev · Pubmed #24136929.

ABSTRACT: BACKGROUND: Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. METHODS: Using genome-wide association studies (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by using the likelihood-ratio test nested in logistic regression models and Ingenuity Pathway Analysis (IPA). RESULTS: After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10(-6)) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10(-4)) in modifying the risk of pancreatic cancer were observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1, and GNAS. None of the individual genes or single-nucleotide polymorphism (SNP) except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10(-7)) at a false discovery rate of 6%. CONCLUSIONS: Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity- and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. IMPACT: A gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer.

7 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.

8 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.

9 Article Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 2013

Obón-Santacana, M / Slimani, N / Lujan-Barroso, L / Travier, N / Hallmans, G / Freisling, H / Ferrari, P / Boutron-Ruault, M C / Racine, A / Clavel, F / Saieva, C / Pala, V / Tumino, R / Mattiello, A / Vineis, P / Argüelles, M / Ardanaz, E / Amiano, P / Navarro, C / Sánchez, M J / Molina Montes, E / Key, T / Khaw, K-T / Wareham, N / Peeters, P H / Trichopoulou, A / Bamia, C / Trichopoulos, D / Boeing, H / Kaaks, R / Katzke, V / Ye, W / Sund, M / Ericson, U / Wirfält, E / Overvad, K / Tjønneland, A / Olsen, A / Skeie, G / Åsli, L A / Weiderpass, E / Riboli, E / Bueno-de-Mesquita, H B / Duell, E J. ·Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. ·Ann Oncol · Pubmed #23857962.

ABSTRACT: BACKGROUND: In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures. PATIENTS AND METHODS: A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes >500,000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously. RESULTS: After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 µg/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 µg/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 µg/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, ≥ 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio. CONCLUSIONS: Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.

10 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.

11 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.

12 Article Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. 2013

Michaud, Dominique S / Izard, Jacques / Wilhelm-Benartzi, Charlotte S / You, Doo-Ho / Grote, Verena A / Tjønneland, Anne / Dahm, Christina C / Overvad, Kim / Jenab, Mazda / Fedirko, Veronika / Boutron-Ruault, Marie Christine / Clavel-Chapelon, Françoise / Racine, Antoine / Kaaks, Rudolf / Boeing, Heiner / Foerster, Jana / Trichopoulou, Antonia / Lagiou, Pagona / Trichopoulos, Dimitrios / Sacerdote, Carlotta / Sieri, Sabina / Palli, Domenico / Tumino, Rosario / Panico, Salvatore / Siersema, Peter D / Peeters, Petra H M / Lund, Eiliv / Barricarte, Aurelio / Huerta, José-María / Molina-Montes, Esther / Dorronsoro, Miren / Quirós, J Ramón / Duell, Eric J / Ye, Weimin / Sund, Malin / Lindkvist, Björn / Johansen, Dorthe / Khaw, Kay-Tee / Wareham, Nick / Travis, Ruth C / Vineis, Paolo / Bueno-de-Mesquita, H Bas / Riboli, Elio. ·Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, USA. ·Gut · Pubmed #22990306.

ABSTRACT: OBJECTIVE: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. DESIGN: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. RESULTS: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). CONCLUSIONS: Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.

13 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.

14 Article The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort. 2012

Grote, Verena A / Nieters, Alexandra / Kaaks, Rudolf / Tjønneland, Anne / Roswall, Nina / Overvad, Kim / Nielsen, Michael R Skjelbo / Clavel-Chapelon, Françoise / Boutron-Ruault, Marie Christine / Racine, Antoine / Teucher, Birgit / Lukanova, Annekatrin / Boeing, Heiner / Drogan, Dagmar / Trichopoulou, Antonia / Trichopoulos, Dimitrios / Lagiou, Pagona / Palli, Domenico / Sieri, Sabina / Tumino, Rosario / Vineis, Paolo / Mattiello, Amalia / Argüelles Suárez, Marcial Vicente / Duell, Eric J / Sánchez, María-José / Dorronsoro, Miren / Huerta Castaño, José María / Barricarte, Aurelio / Jeurnink, Suzanne M / Peeters, Petra H M / Sund, Malin / Ye, Weimin / Regner, Sara / Lindkvist, Björn / Khaw, Kay-Tee / Wareham, Nick / Allen, Naomi E / Crowe, Francesca L / Fedirko, Veronika / Jenab, Mazda / Romaguera, Dora / Siddiq, Afshan / Bueno-de-Mesquita, H Bas / Rohrmann, Sabine. ·Division of Cancer Epidemiology c020, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg, Germany. ·Cancer Epidemiol Biomarkers Prev · Pubmed #22301828.

ABSTRACT: BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). RESULTS: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). CONCLUSIONS AND IMPACT: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations.

15 Article Proanthocyanidins and other flavonoids in relation to pancreatic cancer: a case-control study in Italy. 2012

Rossi, M / Lugo, A / Lagiou, P / Zucchetto, A / Polesel, J / Serraino, D / Negri, E / Trichopoulos, D / La Vecchia, C. ·Department of Epidemiology, Mario Negri Institute for Pharmacological Research, Milan, Italy. marta.rossi@marionegri.it ·Ann Oncol · Pubmed #22052986.

ABSTRACT: BACKGROUND: Four cohort studies have examined the relation between flavonoids and pancreatic cancer risk providing inconsistent results. PATIENTS AND METHODS: We conducted a case-control study between 1991 and 2008 in Northern Italy. Subjects were 326 cases with incident pancreatic cancer and 652 frequency-matched controls (admitted to the same hospitals as cases for acute non-neoplastic conditions) who answered a reproducible and valid food-frequency questionnaire. We computed odds ratios (ORs) using logistic regression models conditioned on gender, age and study center, and adjusted for education, history of diabetes, tobacco smoking, alcohol drinking and energy intake. RESULTS: Proanthocyanidins with three or more mers were inversely related to pancreatic cancer risk. The ORs were similar in all classes of polymers with three or more mers and in their combination (OR for the highest versus the lowest quintile of intake, 0.41; 95% confidence interval 0.24-0.69), and did not substantially change after adjustment for fruit and vegetable consumption, and for vitamin C and folate intakes. Eating an additional portion of fruits rich in proanthocyanidins every day reduced the risk of pancreatic cancer by 25%. CONCLUSION: Dietary proanthocyanidins-mostly present in apples, pears and pulses-may convey some protection against pancreatic cancer risk.

16 Article The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort. 2012

Grote, Verena A / Rohrmann, Sabine / Dossus, Laure / Nieters, Alexandra / Halkjaer, Jytte / Tjønneland, Anne / Overvad, Kim / Stegger, Jakob / Chabbert-Buffet, Nathalie / Boutron-Ruault, Marie-Christine / Clavel-Chapelon, Françoise / Teucher, Birgit / Becker, Susen / Montonen, Jukka / Boeing, Heiner / Trichopoulou, Antonia / Lagiou, Pagona / Trichopoulos, Dimitrios / Palli, Domenico / Sieri, Sabina / Tumino, Rosario / Vineis, Paolo / Mattiello, Amalia / Argüelles, Marcial / Duell, Eric J / Molina-Montes, Esther / Larrañaga, Nerea / Chirlaque, María-Dolores / Gurrea, Aurelio Barricarte / Jeurnink, Suzanne M / Peeters, Petra Hm / Ye, Weimin / Sund, Malin / Lindkvist, Björn / Johansen, Dorthe / Khaw, Kay-Tee / Wareham, Nick / Crowe, Francesca L / Romieu, Isabelle / Rinaldi, Sabina / Jenab, Mazda / Romaguera, Dora / Michaud, Dominique S / Riboli, Elio / Bas Bueno-de-Mesquita, H / Kaaks, Rudolf. ·German Cancer Research Center, Heidelberg, Germany. ·Int J Cancer · Pubmed #21681743.

ABSTRACT: Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.

17 Article Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 2011

Grote, V A / Rohrmann, S / Nieters, A / Dossus, L / Tjønneland, A / Halkjær, J / Overvad, K / Fagherazzi, G / Boutron-Ruault, M C / Morois, S / Teucher, B / Becker, S / Sluik, D / Boeing, H / Trichopoulou, A / Lagiou, P / Trichopoulos, D / Palli, D / Pala, V / Tumino, R / Vineis, P / Panico, S / Rodríguez, L / Duell, E J / Molina-Montes, E / Dorronsoro, M / Huerta, J M / Ardanaz, E / Jeurnink, S M / Beulens, J W J / Peeters, P H M / Sund, M / Ye, W / Lindkvist, B / Johansen, D / Khaw, K T / Wareham, N / Allen, N / Crowe, F / Jenab, M / Romieu, I / Michaud, D S / Riboli, E / Romaguera, D / Bueno-de-Mesquita, H B / Kaaks, R. ·Division of Cancer Epidemiology c020, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. ·Diabetologia · Pubmed #21953276.

ABSTRACT: AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

18 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.

19 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 / Anonymous3240660. ·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.

20 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.

21 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.

22 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.

23 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.