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Pancreatic Neoplasms: HELP
Articles by Debra T. Silverman
Based on 26 articles published since 2009
(Why 26 articles?)
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Between 2009 and 2019, D. Silverman wrote the following 26 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Circulating Leptin and Risk of Pancreatic Cancer: A Pooled Analysis From 3 Cohorts. 2015

Stolzenberg-Solomon, Rachael Z / Newton, Christina C / Silverman, Debra T / Pollak, Michael / Nogueira, Leticia M / Weinstein, Stephanie J / Albanes, Demetrius / Männistö, Satu / Jacobs, Eric J. · ·Am J Epidemiol · Pubmed #26085045.

ABSTRACT: Adiposity is associated with pancreatic cancer; however, the underlying mechanism(s) is uncertain. Leptin is an adipokine involved in metabolic regulation, and obese individuals have higher concentrations. We conducted a pooled, nested case-control study of cohort participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and the Cancer Prevention Study II Nutrition Cohort to investigate whether prediagnostic serum leptin was associated with pancreatic cancer. A total of 731 pancreatic adenocarcinoma cases that occurred between 1986 and 2010 were included (maximum follow-up, 23 years). Incidence density-selected controls (n = 909) were matched to cases by cohort, age, sex, race, and blood draw date. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Sex-specific quintiles were based on the distribution of the controls. Overall, serum leptin was not associated with pancreatic cancer (quintile 5 vs. quintile 1: odds ratio = 1.13, 95% confidence interval: 0.75, 1.71; Ptrend = 0.38). There was a significant interaction by follow-up time (P = 0.003), such that elevated risk was apparent only during follow-up of more than 10 years after blood draw (quintile 5 vs. quintile 1: odds ratio = 2.55, 95% confidence interval: 1.23, 5.27; Ptrend = 0.004). Our results support an association between increasing leptin concentration and pancreatic cancer; however, long follow-up is necessary to observe the relationship. Subclinical disease may explain the lack of association during early follow-up.

2 Review Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies. 2014

Genkinger, J M / Wang, M / Li, R / Albanes, D / Anderson, K E / Bernstein, L / van den Brandt, P A / English, D R / Freudenheim, J L / Fuchs, C S / Gapstur, S M / Giles, G G / Goldbohm, R A / Håkansson, N / Horn-Ross, P L / Koushik, A / Marshall, J R / McCullough, M L / Miller, A B / Robien, K / Rohan, T E / Schairer, C / Silverman, D T / Stolzenberg-Solomon, R Z / Virtamo, J / Willett, W C / Wolk, A / Ziegler, R G / Smith-Warner, S A. ·Department of Epidemiology, Mailman School of Public Health, Columbia University, New York jg3081@columbia.edu. · Department of Epidemiology, Harvard School of Public Health, Boston Department of Biostatistics, Harvard School of Public Health, Boston. · Department of Epidemiology, Harvard School of Public Health, Boston. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda. · Division of Epidemiology and Community Health, School of Public Health, Masonic Cancer Center, University of Minnesota, Minneapolis. · Division of Cancer Etiology, Department of Population Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, USA. · Department of Epidemiology, School for Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands. · Cancer Epidemiology Centre, Cancer Council of Victoria, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. · Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo. · Division of Medical Oncology, Dana-Farber Cancer Institute, Boston Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. · Epidemiology Research Program, American Cancer Society, Atlanta, USA. · Department of Prevention and Health, TNO Quality of Life, Leiden, The Netherlands. · Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. · Cancer Prevention Institute of California, Fremont, USA. · Department of Social and Preventive Medicine, University of Montreal, Montreal. · Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. · Department of Epidemiology and Biostatistics, School of Public Health and Health Services, George Washington University, Washington, DC. · Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, USA. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. · Department of Epidemiology, Harvard School of Public Health, Boston Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston Department of Nutrition, Harvard School of Public Health, Boston, USA. · Department of Epidemiology, Harvard School of Public Health, Boston Department of Nutrition, Harvard School of Public Health, Boston, USA. ·Ann Oncol · Pubmed #24631943.

ABSTRACT: Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

3 Review Occupational risk factors and pancreatic cancer: a review of recent findings. 2012

Andreotti, Gabriella / Silverman, Debra T. ·Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. andreotg@mail.nih.gov ·Mol Carcinog · Pubmed #22162234.

ABSTRACT: Several occupational exposures have been linked to excess risk of pancreatic cancer; however, most associations are not well established. The objective of this review article is to report on the more recently published studies (1998-2010), and provide a summary of the most consistently reported occupational risk factors for pancreatic cancer, including exposure to chlorinated hydrocarbon compounds, pesticides, polycyclic aromatic hydrocarbons (PAHs), metals, nitrosamines, radiation, various airborne particles, and employment in sedentary occupations. We conclude that the strongest and most consistent findings linking occupational exposures with pancreatic cancer risk to date are for chlorinated hydrocarbons and PAHs.

4 Article Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. 2018

Klein, Alison P / Wolpin, Brian M / Risch, Harvey A / Stolzenberg-Solomon, Rachael Z / Mocci, Evelina / Zhang, Mingfeng / Canzian, Federico / Childs, Erica J / Hoskins, Jason W / Jermusyk, Ashley / Zhong, Jun / Chen, Fei / Albanes, Demetrius / Andreotti, Gabriella / Arslan, Alan A / Babic, Ana / Bamlet, William R / Beane-Freeman, Laura / Berndt, Sonja I / Blackford, Amanda / Borges, Michael / Borgida, Ayelet / Bracci, Paige M / Brais, Lauren / Brennan, Paul / Brenner, Hermann / Bueno-de-Mesquita, Bas / Buring, Julie / Campa, Daniele / Capurso, Gabriele / Cavestro, Giulia Martina / Chaffee, Kari G / Chung, Charles C / Cleary, Sean / Cotterchio, Michelle / Dijk, Frederike / Duell, Eric J / Foretova, Lenka / Fuchs, Charles / Funel, Niccola / Gallinger, Steven / M Gaziano, J Michael / Gazouli, Maria / Giles, Graham G / Giovannucci, Edward / Goggins, Michael / Goodman, Gary E / Goodman, Phyllis J / Hackert, Thilo / Haiman, Christopher / Hartge, Patricia / Hasan, Manal / Hegyi, Peter / Helzlsouer, Kathy J / Herman, Joseph / Holcatova, Ivana / Holly, Elizabeth A / Hoover, Robert / Hung, Rayjean J / Jacobs, Eric J / Jamroziak, Krzysztof / Janout, Vladimir / Kaaks, Rudolf / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Kooperberg, Charles / Kulke, Matthew H / Kupcinskas, Juozas / Kurtz, Robert J / Laheru, Daniel / Landi, Stefano / Lawlor, Rita T / Lee, I-Min / LeMarchand, Loic / Lu, Lingeng / Malats, Núria / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Mohelníková-Duchoňová, Beatrice / Neale, Rachel E / Neoptolemos, John P / Oberg, Ann L / Olson, Sara H / Orlow, Irene / Pasquali, Claudio / Patel, Alpa V / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Real, Francisco X / Rothman, Nathaniel / Scelo, Ghislaine / Sesso, Howard D / Severi, Gianluca / Shu, Xiao-Ou / Silverman, Debra / Smith, Jill P / Soucek, Pavel / Sund, Malin / Talar-Wojnarowska, Renata / Tavano, Francesca / Thornquist, Mark D / Tobias, Geoffrey S / Van Den Eeden, Stephen K / Vashist, Yogesh / Visvanathan, Kala / Vodicka, Pavel / Wactawski-Wende, Jean / Wang, Zhaoming / Wentzensen, Nicolas / White, Emily / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Zheng, Wei / Kraft, Peter / Li, Donghui / Chanock, Stephen / Obazee, Ofure / Petersen, Gloria M / Amundadottir, Laufey T. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. aklein1@jhmi.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. aklein1@jhmi.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, 06520, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, 10016, USA. · Department of Population Health, New York University School of Medicine, New York, NY, 10016, USA. · Department of Environmental Medicine, New York University School of Medicine, New York, NY, 10016, USA. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, M5G 1×5, Canada. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 94158, USA. · International Agency for Research on Cancer (IARC), 69372, Lyon, France. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, 3584 CX, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. · Department of Biology, University of Pisa, 56126, Pisa, Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, 00185, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. · Cancer Care Ontario, University of Toronto, Toronto, Ontario, M5G 2L7, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7, Canada. · Department of Pathology, Academic Medical Center, University of Amsterdam, 1007 MB, Amsterdam, The Netherlands. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, 08908, Spain. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 65653, Brno, Czech Republic. · Yale Cancer Center, New Haven, CT, 06510, USA. · Department of Translational Research and The New Technologies in Medicine and Surgery, University of Pisa, 56126, Pisa, Italy. · Division of Aging, Brigham and Women's Hospital, Boston, MA, 02115, USA. · Boston VA Healthcare System, Boston, MA, 02132, USA. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 106 79, Athens, Greece. · Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. · SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. · Department of General Surgery, University Hospital Heidelberg, 69120, Heidelberg, Germany. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, USA. · Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, 77230, USA. · First Department of Medicine, University of Szeged, 6725, Szeged, Hungary. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. · Institute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, 150 06, Prague 5, Czech Republic. · Epidemiology Research Program, American Cancer Society, Atlanta, GA, 30303, USA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776, Warsaw, Poland. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, 701 03, Ostrava, Czech Republic. · Faculty of Medicine, University of Olomouc, 771 47, Olomouc, Czech Republic. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SP, UK. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. · ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), 08003, Barcelona, Spain. · CIBER Epidemiología y Salud Pública (CIBERESP), 08003, Barcelona, Spain. · Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, 08003, Barcelona, Spain. · Universitat Pompeu Fabra (UPF), 08002, Barcelona, Spain. · Department of Gastroenterology, Lithuanian University of Health Sciences, 44307, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, 37134, Verona, Italy. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain. · CIBERONC, 28029, Madrid, Spain. · Oncology Department, ASL1 Massa Carrara, Carrara, 54033, Italy. · Department of Public Health Solutions, National Institute for Health and Welfare, 00271, Helsinki, Finland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, 775 20, Olomouc, Czech Republic. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia. · Department of General Surgery, University of Heidelburg, Heidelberg, Germany. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, 35124, Padua, Italy. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, 40138, Bologna, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, 28029, Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08002, Barcelona, Spain. · Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, 94800, Villejuif, France. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. · Department of Medicine, Georgetown University, Washington, 20057, USA. · Laboratory for Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00, Pilsen, Czech Republic. · Department of Surgical and Perioperative Sciences, Umeå University, 901 85, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, 90-647, Łodz, Poland. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy. · Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA. · Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, 20246, Hamburg, Germany. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20, Prague 4, Czech Republic. · Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, 14214, USA. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. · Department of Epidemiology, University of Washington, Seattle, WA, 98195, USA. · Perlmutter Cancer Center, New York University School of Medicine, New York, NY, 10016, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. amundadottirl@mail.nih.gov. ·Nat Commun · Pubmed #29422604.

ABSTRACT: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10

5 Article Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking? 2017

Nogueira, Leticia M / Newton, Christina C / Pollak, Michael / Silverman, Debra T / Albanes, Demetrius / Männistö, Satu / Weinstein, Stephanie J / Jacobs, Eric J / Stolzenberg-Solomon, Rachael Z. ·Texas Cancer Registry, Department of State Health Services, Austin, Texas. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland. · Epidemiology Research Program, American Cancer Society, Atlanta Georgia. · Department of Oncology, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Quebec, Canada. · Department of Health, National Institute for Health and Welfare, Helsinki, Finland. · Epidemiology Research Program, American Cancer Society, Atlanta Georgia. rs221z@nih.gov Eric.jacobs@cancer.org. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Rockville, Maryland. rs221z@nih.gov Eric.jacobs@cancer.org. ·Cancer Epidemiol Biomarkers Prev · Pubmed #28096201.

ABSTRACT:

6 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.

7 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.

8 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.

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

Wang, Zhaoming / Zhu, Bin / Zhang, Mingfeng / Parikh, Hemang / Jia, Jinping / Chung, Charles C / Sampson, Joshua N / Hoskins, Jason W / Hutchinson, Amy / Burdette, Laurie / Ibrahim, Abdisamad / Hautman, Christopher / Raj, Preethi S / Abnet, Christian C / Adjei, Andrew A / Ahlbom, Anders / Albanes, Demetrius / Allen, Naomi E / Ambrosone, Christine B / Aldrich, Melinda / Amiano, Pilar / Amos, Christopher / Andersson, Ulrika / Andriole, Gerald / Andrulis, Irene L / Arici, Cecilia / Arslan, Alan A / Austin, Melissa A / Baris, Dalsu / Barkauskas, Donald A / Bassig, Bryan A / Beane Freeman, Laura E / Berg, Christine D / Berndt, Sonja I / Bertazzi, Pier Alberto / Biritwum, Richard B / Black, Amanda / Blot, William / Boeing, Heiner / Boffetta, Paolo / Bolton, Kelly / Boutron-Ruault, Marie-Christine / Bracci, Paige M / Brennan, Paul / Brinton, Louise A / Brotzman, Michelle / Bueno-de-Mesquita, H Bas / Buring, Julie E / Butler, Mary Ann / Cai, Qiuyin / Cancel-Tassin, Geraldine / Canzian, Federico / Cao, Guangwen / Caporaso, Neil E / Carrato, Alfredo / Carreon, Tania / Carta, Angela / Chang, Gee-Chen / Chang, I-Shou / Chang-Claude, Jenny / Che, Xu / Chen, Chien-Jen / Chen, Chih-Yi / Chen, Chung-Hsing / Chen, Constance / Chen, Kuan-Yu / Chen, Yuh-Min / Chokkalingam, Anand P / Chu, Lisa W / Clavel-Chapelon, Francoise / Colditz, Graham A / Colt, Joanne S / Conti, David / Cook, Michael B / Cortessis, Victoria K / Crawford, E David / Cussenot, Olivier / Davis, Faith G / De Vivo, Immaculata / Deng, Xiang / Ding, Ti / Dinney, Colin P / Di Stefano, Anna Luisa / Diver, W Ryan / Duell, Eric J / Elena, Joanne W / Fan, Jin-Hu / Feigelson, Heather Spencer / Feychting, Maria / Figueroa, Jonine D / Flanagan, Adrienne M / Fraumeni, Joseph F / Freedman, Neal D / Fridley, Brooke L / Fuchs, Charles S / Gago-Dominguez, Manuela / Gallinger, Steven / Gao, Yu-Tang / Gapstur, Susan M / Garcia-Closas, Montserrat / Garcia-Closas, Reina / Gastier-Foster, Julie M / Gaziano, J Michael / Gerhard, Daniela S / Giffen, Carol A / Giles, Graham G / Gillanders, Elizabeth M / Giovannucci, Edward L / Goggins, Michael / Gokgoz, Nalan / Goldstein, Alisa M / Gonzalez, Carlos / Gorlick, Richard / Greene, Mark H / Gross, Myron / Grossman, H Barton / Grubb, Robert / Gu, Jian / Guan, Peng / Haiman, Christopher A / Hallmans, Goran / Hankinson, Susan E / Harris, Curtis C / Hartge, Patricia / Hattinger, Claudia / Hayes, Richard B / He, Qincheng / Helman, Lee / Henderson, Brian E / Henriksson, Roger / Hoffman-Bolton, Judith / Hohensee, Chancellor / Holly, Elizabeth A / Hong, Yun-Chul / Hoover, Robert N / Hosgood, H Dean / Hsiao, Chin-Fu / Hsing, Ann W / Hsiung, Chao Agnes / Hu, Nan / Hu, Wei / Hu, Zhibin / Huang, Ming-Shyan / Hunter, David J / Inskip, Peter D / Ito, Hidemi / Jacobs, Eric J / Jacobs, Kevin B / Jenab, Mazda / Ji, Bu-Tian / Johansen, Christoffer / Johansson, Mattias / Johnson, Alison / Kaaks, Rudolf / Kamat, Ashish M / Kamineni, Aruna / Karagas, Margaret / Khanna, Chand / Khaw, Kay-Tee / Kim, Christopher / Kim, In-Sam / Kim, Jin Hee / Kim, Yeul Hong / Kim, Young-Chul / Kim, Young Tae / Kang, Chang Hyun / Jung, Yoo Jin / Kitahara, Cari M / Klein, Alison P / Klein, Robert / Kogevinas, Manolis / Koh, Woon-Puay / Kohno, Takashi / Kolonel, Laurence N / Kooperberg, Charles / Kratz, Christian P / Krogh, Vittorio / Kunitoh, Hideo / Kurtz, Robert C / Kurucu, Nilgun / Lan, Qing / Lathrop, Mark / Lau, Ching C / Lecanda, Fernando / Lee, Kyoung-Mu / Lee, Maxwell P / Le Marchand, Loic / Lerner, Seth P / Li, Donghui / Liao, Linda M / Lim, Wei-Yen / Lin, Dongxin / Lin, Jie / Lindstrom, Sara / Linet, Martha S / Lissowska, Jolanta / Liu, Jianjun / Ljungberg, Börje / Lloreta, Josep / Lu, Daru / Ma, Jing / Malats, Nuria / Mannisto, Satu / Marina, Neyssa / Mastrangelo, Giuseppe / Matsuo, Keitaro / McGlynn, Katherine A / McKean-Cowdin, Roberta / McNeill, Lorna H / McWilliams, Robert R / Melin, Beatrice S / Meltzer, Paul S / Mensah, James E / Miao, Xiaoping / Michaud, Dominique S / Mondul, Alison M / Moore, Lee E / Muir, Kenneth / Niwa, Shelley / Olson, Sara H / Orr, Nick / Panico, Salvatore / Park, Jae Yong / Patel, Alpa V / Patino-Garcia, Ana / Pavanello, Sofia / Peeters, Petra H M / Peplonska, Beata / Peters, Ulrike / Petersen, Gloria M / Picci, Piero / Pike, Malcolm C / Porru, Stefano / Prescott, Jennifer / Pu, Xia / Purdue, Mark P / Qiao, You-Lin / Rajaraman, Preetha / Riboli, Elio / Risch, Harvey A / Rodabough, Rebecca J / Rothman, Nathaniel / Ruder, Avima M / Ryu, Jeong-Seon / Sanson, Marc / Schned, Alan / Schumacher, Fredrick R / Schwartz, Ann G / Schwartz, Kendra L / Schwenn, Molly / Scotlandi, Katia / Seow, Adeline / Serra, Consol / Serra, Massimo / Sesso, Howard D / Severi, Gianluca / Shen, Hongbing / Shen, Min / Shete, Sanjay / Shiraishi, Kouya / Shu, Xiao-Ou / Siddiq, Afshan / Sierrasesumaga, Luis / Sierri, Sabina / Loon Sihoe, Alan Dart / Silverman, Debra T / Simon, Matthias / Southey, Melissa C / Spector, Logan / Spitz, Margaret / Stampfer, Meir / Stattin, Par / Stern, Mariana C / Stevens, Victoria L / Stolzenberg-Solomon, Rachael Z / Stram, Daniel O / Strom, Sara S / Su, Wu-Chou / Sund, Malin / Sung, Sook Whan / Swerdlow, Anthony / Tan, Wen / Tanaka, Hideo / Tang, Wei / Tang, Ze-Zhang / Tardon, Adonina / Tay, Evelyn / Taylor, Philip R / Tettey, Yao / Thomas, David M / Tirabosco, Roberto / Tjonneland, Anne / Tobias, Geoffrey S / Toro, Jorge R / Travis, Ruth C / Trichopoulos, Dimitrios / Troisi, Rebecca / Truelove, Ann / Tsai, Ying-Huang / Tucker, Margaret A / Tumino, Rosario / Van Den Berg, David / Van Den Eeden, Stephen K / Vermeulen, Roel / Vineis, Paolo / Visvanathan, Kala / Vogel, Ulla / Wang, Chaoyu / Wang, Chengfeng / Wang, Junwen / Wang, Sophia S / Weiderpass, Elisabete / Weinstein, Stephanie J / Wentzensen, Nicolas / Wheeler, William / White, Emily / Wiencke, John K / Wolk, Alicja / Wolpin, Brian M / Wong, Maria Pik / Wrensch, Margaret / Wu, Chen / Wu, Tangchun / Wu, Xifeng / Wu, Yi-Long / Wunder, Jay S / Xiang, Yong-Bing / Xu, Jun / Yang, Hannah P / Yang, Pan-Chyr / Yatabe, Yasushi / Ye, Yuanqing / Yeboah, Edward D / Yin, Zhihua / Ying, Chen / Yu, Chong-Jen / Yu, Kai / Yuan, Jian-Min / Zanetti, Krista A / Zeleniuch-Jacquotte, Anne / Zheng, Wei / Zhou, Baosen / Mirabello, Lisa / Savage, Sharon A / Kraft, Peter / Chanock, Stephen J / Yeager, Meredith / Landi, Maria Terese / Shi, Jianxin / Chatterjee, Nilanjan / Amundadottir, Laufey T. ·Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA. · Division of Cancer Epidemiology and Genetics. · Korle Bu Teaching Hospital, PO BOX 77, Accra, Ghana, University of Ghana Medical School, PO Box 4236, Accra, Ghana. · Unit of Epidemiology, Institute of Environmental Medicine. · Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK. · Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA. · Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain, CIBERESP, CIBER Epidemiologia y Salud Publica, Madrid, Spain. · Geisel School of Medicine at Dartmouth, Hanover, NH, USA. · Department of Radiation Sciences, Oncology. · Division of Urologic Surgery, Washington University School of Medicine, St Louis, MO, USA. · Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, ON, Canada. · Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy. · Department of Obstetrics and Gynecology and Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA. · Department of Epidemiology, University of Washington, Seattle, WA, USA. · Department of Preventive Medicine, Biostatistics Division, Keck School of Medicine and. · Division of Cancer Epidemiology and Genetics, Division of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA. · Division of Cancer Prevention. · Department of Clinical Sciences and Community Health, University of Milan, Department of Preventive Medicine, Fondazione IRCCS Ca' Granda Policlinico Hospital, Milan, Italy. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA, International Epidemiology Institute, Rockville, MD, USA. · Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. · Institute for Translational Epidemiology, Hematology 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Epidemiology and Public Health, Yong Loo Lin School of Medicine and Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, College of Medical Science and Technology, Taipei Medical University, Taiwan. · School of Public Health, University of California, Berkeley, CA, USA. · Cancer Prevention Institute of California, Fremont, CA, USA. · Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. · Washington University School of Medicine, St Louis, MO, USA. · Urologic Oncology, University of Colorado, Aurora, CO, USA. · CeRePP, Paris, France, AP-HP, Department of Urology, Tenon Hospital, GHU-Est, Paris, France, UPMC Univ Paris 06, GRC n°5, ONCOTYPE-URO, Paris, France. · Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, AB, Canada T6G 2R3. · Program in Molecular and Genetic Epidemiology, Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Shanxi Cancer Hospital, Taiyuan, Shanxi, People's Republic of China. · Department of Urology. · Service de Neurologie Mazarin, GH Pitie-Salpetriere, APHP, and UMR 975 INSERM-UPMC, CRICM, Paris, France. · Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. · Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, Bethesda, MD, USA. · Shanghai Cancer Institute, Shanghai, People's Republic of China. · Institute for Health Research, Kaiser Permanente, Denver, CO, USA. · UCL Cancer Institute, Huntley Street, London WC1E 6BT, UK, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK. · Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, Channing Laboratory, Department of Medicine. · Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain. · Samuel Lunenfeld Research Institute and. · Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotaong University School of Medicine, Shanghai, China. · Division of Cancer Epidemiology and Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK. · Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain. · Nationwide Children's Hospital, and The Ohio State University Department of Pathology and Pediatrics, Columbus, OH, USA. · Division of Preventive Medicine, Department of Medicine and Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, MA, USA. · Office of Cancer Genomics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. · Information Management Services Inc., Calverton, MD, USA. · Cancer Epidemiology Centre, The Cancer Council Victoria & Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Victoria, Australia. · Division of Cancer Control and Population Sciences and. · Program in Molecular and Genetic Epidemiology, Department of Nutrition and. · Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. · Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain. · Albert Einstein College of Medicine, The Children's Hospital at Montefiore, Bronx, NY, USA. · Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA. · Department of Urology, Washington University School of Medicine, St Louis, MO, USA. · Department of Epidemiology. · Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. · Department of Public Health and Clinical Medicine/Nutritional Research. · Channing Laboratory, Department of Medicine. · Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. · Laboratory of Experimental Oncology, Orthopaedic Rizzoli Institute, Bologna, Italy. · Division of Cancer Epidemiology and Genetics, Department of Population Health, New York University Langone Medical Center and Department of Environmental Medicine, New York University Langone Medical Center, New York University Cancer Institute, New York, NY, USA. · Center for Cancer Research and. · Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea, Department of Preventive Medicine and. · Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. · Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences and Taiwan Lung Cancer Tissue/Specimen Information Resource Center, National Health Research Institutes, Zhunan, Taiwan. · Cancer Prevention Institute of California, Fremont, CA, USA, Stanford Cancer Institute, Stanford University, Stanford, CA, USA. · Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences and. · Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, Nanjing, China. · Program in Molecular and Genetic Epidemiology, Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Broad Institute of Harvard and MIT, Cambridge, MA, USA. · Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Bioinformed, LLC, Gaithersburg, MD, USA. · Department of Oncology, Finsen Center, Rigshospitalet, Copenhagen, Denmark, Unit of Survivorship, Danish Cancer Society Research Center, Copenhagen, Denmark. · International Agency for Research on Cancer (IARC-WHO), Lyon, France, Department of Public Health and Clinical Medicine. · Vermont Cancer Registry, Burlington, VT, USA. · Group Health Research Institute, Seattle, WA, USA. · School of Clinical Medicine, University of Cambridge, UK. · Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. · Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. · Genomic Research Center for Lung and Breast/Ovarian Cancers, Korea University Anam Hospital, Seoul, Republic of Korea, Department of Internal Medicine and Division of Brain and Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea. · Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-eup, Republic of Korea. · Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. · Department of Oncology, Department of Pathology and Department of Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Department of Medicine and. · Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, National School of Public Health, Athens, Greece. · Duke-NUS Graduate Medical School, Singapore, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore. · Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. · Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan, Department of Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan. · Department of Pediatric Oncology, A.Y. Ankara Oncology Training and Research Hospital, Yenimahalle- Ankara, Turkey. · Centre National de Genotypage, IG/CEA, Evry Cedex, France, Centre d'Étude du Polymorphism Humain (CEPH), Paris, France. · Texas Children's Cancer and Hematology Centers. · Department of Pediatrics, University Clinic of Navarra, Universidad de Navarra, Pamplona, Spain. · Department of Preventive Medicine and Department of Environmental Health, Korea National Open University, Seoul, Republic of Korea. · Scott Department of Urology and. · Department of Gastrointestinal Medical Oncology. · Saw Swee Hock School of Public Health, National University of Singapore, Singapore. · State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Cancer Epidemiology and Prevention, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland. · Human Genetics Division, Genome Institute of Singapore, Singapore, School of Life Sciences, Anhui Medical University, Hefei, China. · Department of Surgical and Perioperative Sciences, Urology and Andrology and. · CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. · Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. · Department of Medicine, Channing Division of Network Medicine and Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Centro Nacional de Investigaciones Oncologicas, Melchor Fernández Almagro, 3, Madrid E-28029, Spain. · National Institute for Health and Welfare, Helsinki, Finland. · Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA, USA. · Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padua, Italy. · Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan, Department of Preventive Medicine, Kyushu University Faculty of Medical Scicence, Fukuoka, Japan. · Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, and Center for Community-Engaged Translational Research, Duncan Family Institute and. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. · Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, RI, USA. · Health Sciences Research Institute, University of Warwick, Coventry, UK. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Complex Traits Genetics Team and. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Department of Biochemistry and Department of Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea, Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea. · Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Utrecht, The Netherlands, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Nofer Institute of Occupational Medicine, Lodz, Poland. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Yale School of Public Health, New Haven, CT, USA. · Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea. · Karmanos Cancer Institute and Department of Oncology and. · Karmanos Cancer Institute and Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA. · Maine Cancer Registry, Augusta, ME, USA. · Centre for Research in Occupational Health, Universitat Pompeu Fabra, Barcelona, Spain, CIBER of Epidemiology and Public Health (CIBERESP). · Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA. · Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK. · Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Surgery, Division of Cardiothoracic Surgery, Queen Mary Hospital, Hong Kong, China. · Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany. · Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia. · University of Minnesota, Minneapolis, MN, USA. · Dan L. Duncan Center, Baylor College of Medicine, Houston, TX, USA. · Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. · Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden. · Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, Seoul, South Korea. · Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK, Division of Breast Cancer Research, Institute of Cancer Research, London, UK. · Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain. · Sir Peter MacCallum Department of Oncology, University of Melbourne, St Andrew's Place, East Melbourne, VIC, Australia. · Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. · Department of Pulmonary Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan. · Cancer Registry Associazione Iblea Ricerca Epidemiologica, Onlus and Asp Ragusa, Ragusa Italy. · Kaiser Permanente Northern California, Oakland, CA, USA. · Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. · Imperial College, London, UK, Human Genetics Foundation (HuGeF), Torino Italy. · National Research Centre for the Working Environment, Copenhagen, Denmark, National Food Institute, Technical University of Denmark, Soborg, Denmark. · Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. · Division of Cancer Etiology, Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, CA, USA. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Department of Research, Cancer Registry of Norway, Oslo, Norway, Department of Medical Epidemiology and Biostatistics and Samfundet Folkhälsan, Helsinki, Finland. · University of California San Francisco, San Francisco, CA, USA. · Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Pathology and. · Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. · School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China. · Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital and. · University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA and. · Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA. · Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. · Division of Cancer Epidemiology and Genetics, amundadottirl@mail.nih.gov. ·Hum Mol Genet · Pubmed #25027329.

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

10 Article Serum transforming growth factor-β1 and risk of pancreatic cancer in three prospective cohort studies. 2014

Jacobs, Eric J / Newton, Christina C / Silverman, Debra T / Nogueira, Leticia M / Albanes, Demetrius / Männistö, Satu / Pollak, Michael / Stolzenberg-Solomon, Rachael Z. ·Epidemiology Research Program, American Cancer Society, National Home Office, 250 Williams Street, Atlanta, GA, 30303-1002, USA, ejacobs@cancer.org. ·Cancer Causes Control · Pubmed #24913781.

ABSTRACT: PURPOSE: Clinically evident chronic pancreatitis is a strong risk factor for pancreatic cancer. A small Japanese cohort study previously reported that pre-diagnostic serum transforming growth factor-β1 (TGF-β1) concentration, a potential marker of subclinical pancreatic inflammation, was associated with higher risk of pancreatic cancer. We further explored this association in a larger prospective study. METHODS: Serum TGF-β1 concentrations were measured in pre-diagnostic samples from 729 pancreatic cancer cases and 907 matched controls from a cohort of Finnish male smokers (the Alpa-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study) and two cohorts of US men and women, the Cancer Prevention Study-II and the Prostate Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Multivariable-adjusted odds ratios (ORs) were estimated using conditional logistic regression. RESULTS: Overall, serum TGF-β1 concentration was not associated with a clear increase in pancreatic cancer risk (OR 1.36, 95 % confidence interval (CI) 0.98-1.88 for highest vs. lowest quintile, p trend = 0.20). However, this association differed significantly by follow-up time (p = 0.02). Serum TGF-β1 concentration was not associated with risk during the first 10 years of follow-up, but was associated with higher risk during follow-up after 10 years (OR 2.13, 95 % CI 1.23-3.68 for highest vs. lowest quintile, p trend = 0.001). During follow-up after 10 years, serum TGF-β1 was associated with higher risk only in the ATBC cohort, although most subjects were from ATBC during this time period and statistical evidence for heterogeneity across cohorts was limited (p = 0.14). CONCLUSIONS: These results suggest that high serum TGF-β1 may be associated with increased risk of pancreatic cancer although a long follow-up period may be needed to observe this association.

11 Article Serum immunoglobulin e and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. 2014

Olson, Sara H / Hsu, Meier / Wiemels, Joseph L / Bracci, Paige M / Zhou, Mi / Patoka, Joseph / Reisacher, William R / Wang, Julie / Kurtz, Robert C / Silverman, Debra T / Stolzenberg-Solomon, Rachael Z. ·Authors' Affiliations: Department of Epidemiology and Biostatistics; olsons@mskcc.org. · Authors' Affiliations: Department of Epidemiology and Biostatistics; · Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, California; · Department of Otolaryngology-Head and Neck Surgery, Weill Cornell Medical College, New York, New York; · Division of Pediatric Allergy and Immunology, Mt. Sinai Medical Center; · Department of Medicine, Memorial Sloan Kettering Cancer Center; · Occupational and Environmental Epidemiology Branch; and. · Branch of Nutritional Epidemiology, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. ·Cancer Epidemiol Biomarkers Prev · Pubmed #24718282.

ABSTRACT: Epidemiologic studies have consistently found that self-reported allergies are associated with reduced risk of pancreatic cancer. Our aim was to prospectively assess the relationship between serum immunoglobulin E (IgE), a marker of allergy, and risk. This nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) included subjects enrolled in 1994 to 2001 and followed through 2010. There were 283 cases of pancreatic cancer and 544 controls matched on age, gender, race, and calendar date of blood draw. Using the ImmunoCAP system, we measured total IgE (normal, borderline, elevated), IgE to respiratory allergens, and IgE to food allergens (negative or positive) in serum collected at baseline. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We assessed interactions with age, gender, smoking, body mass index, and time between randomization and case diagnosis. Overall, there was no association between the IgE measures and risk. We found a statistically significant interaction by baseline age: in those aged ≥65 years, elevated risks were observed for borderline total IgE (OR, 1.43; 95% CI, 0.88-2.32) and elevated total IgE (OR, 1.98; 95% CI, 1.16-3.37) and positive IgE to food allergens (OR, 2.83; 95% CI, 1.29-6.20); among participants <65 years, ORs were <1. Other interactions were not statistically significant. The reduced risk of pancreatic cancer associated with self-reported allergies is not reflected in serum IgE.

12 Article Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort. 2013

Stolzenberg-Solomon, Rachael Z / Schairer, Catherine / Moore, Steve / Hollenbeck, Albert / Silverman, Debra T. ·Branches of Nutritional Epidemiology, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD. ·Am J Clin Nutr · Pubmed #23985810.

ABSTRACT: BACKGROUND: The association of excess body weight across a lifetime with pancreatic cancer has not been examined extensively. OBJECTIVE: We determined the association for body mass index (BMI) at different ages and adiposity duration and gain with incident pancreatic adenocarcinoma in the NIH-AARP Diet and Health Study cohort. DESIGN: Participants aged 50-71 y completed questionnaires at baseline (1995-1996) and 6 months later that queried height and weight history. We calculated HRs and 95% CIs by using Cox proportional hazards models adjusted for age, smoking, sex, and intakes of energy and total fat. RESULTS: Over an average follow-up of 10.5 y, 1206 and 2122 pancreatic cancer cases were identified in the subcohort who completed the second questionnaire (n = 273,975) and the baseline cohort (n = 501,698), respectively. Compared with normal weight, overweight or obesity at ages 18, 35, 50, or >50 y (baseline BMI) was significantly associated with pancreatic cancer, with HRs ranging from 1.15 to 1.53. A longer duration of BMI (in kg/m(2)) >25.0 was significantly associated with pancreatic cancer (overall HR per 10-y increment of duration: 1.06; 95% CI: 1.02, 1.09), with individuals who reported diabetes having the greatest risk (HR per 10-y increment of duration: 1.18; 95% CI: 1.05, 1.32; P-interaction = 0.01) and rates. A substantial gain in adiposity (>10 kg/m(2)) after age 50 y was significantly associated with increased pancreatic cancer risk. The etiologic fraction of pancreatic cancer explained by adiposity at any age was 14% overall and 21% in never smokers. CONCLUSION: Overweight and obesity at any age are associated with increased pancreatic cancer.

13 Article Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. 2013

Olson, Sara H / Hsu, Meier / Satagopan, Jaya M / Maisonneuve, Patrick / Silverman, Debra T / Lucenteforte, Ersilia / Anderson, Kristin E / Borgida, Ayelet / Bracci, Paige M / Bueno-de-Mesquita, H Bas / Cotterchio, Michelle / Dai, Qi / Duell, Eric J / Fontham, Elizabeth H / Gallinger, Steven / Holly, Elizabeth A / Ji, Bu-Tian / Kurtz, Robert C / La Vecchia, Carlo / Lowenfels, Albert B / Luckett, Brian / Ludwig, Emmy / Petersen, Gloria M / Polesel, Jerry / Seminara, Daniela / Strayer, Lori / Talamini, Renato / Anonymous6651223. ·Department of Epidemiology and Biostatistics, 307 East 63rd Street, New York, NY 10065, USA. olsons@mskcc.org ·Am J Epidemiol · Pubmed #23820785.

ABSTRACT: In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.

14 Article Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer. 2013

Kohaar, Indu / Porter-Gill, Patricia / Lenz, Petra / Fu, Yi-Ping / Mumy, Adam / Tang, Wei / Apolo, Andrea B / Rothman, Nathaniel / Baris, Dalsu / Schned, Alan R / Ylaya, Kris / Schwenn, Molly / Johnson, Alison / Jones, Michael / Kida, Masatoshi / Silverman, Debra T / Hewitt, Stephen M / Moore, Lee E / Prokunina-Olsson, Ludmila. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 8717 Grovemont Cir, Bethesda, MD 20892-4605, USA. ·J Natl Cancer Inst · Pubmed #23266392.

ABSTRACT: A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10(-11); n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10(-5); n = 173) and T1 (P = 2.64×10(-5); n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.

15 Article Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). 2012

Duell, E J / Lucenteforte, E / Olson, S H / Bracci, P M / Li, D / Risch, H A / Silverman, D T / Ji, B T / Gallinger, S / Holly, E A / Fontham, E H / Maisonneuve, P / Bueno-de-Mesquita, H B / Ghadirian, P / Kurtz, R C / Ludwig, E / Yu, H / Lowenfels, A B / Seminara, D / Petersen, G M / La Vecchia, C / Boffetta, P. ·Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. eduell@iconcologia.net ·Ann Oncol · Pubmed #22767586.

ABSTRACT: BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

16 Article Pancreatic cancer risk and levels of trace elements. 2012

Amaral, André F S / Porta, Miquel / Silverman, Debra T / Milne, Roger L / Kogevinas, Manolis / Rothman, Nathaniel / Cantor, Kenneth P / Jackson, Brian P / Pumarega, José A / López, Tomàs / Carrato, Alfredo / Guarner, Luisa / Real, Francisco X / Malats, Núria. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, Madrid, Spain. ·Gut · Pubmed #22184070.

ABSTRACT: BACKGROUND AND AIMS: Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk. METHODS: The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression. RESULTS: Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; p(trend)=5×10(-6)), arsenic (OR 2.02, 95% CI 1.08 to 3.78; p(trend)=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; p(trend)=3×10(-5)) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; p(trend)=8×10(-11)) and nickel (OR 0.27, 95% CI 0.12 to 0.59; p(trend)=2×10(-4)) were inversely associated with the risk of EPC. CONCLUSION: Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

17 Article Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). 2012

Bosetti, C / Lucenteforte, E / Silverman, D T / Petersen, G / Bracci, P M / Ji, B T / Negri, E / Li, D / Risch, H A / Olson, S H / Gallinger, S / Miller, A B / Bueno-de-Mesquita, H B / Talamini, R / Polesel, J / Ghadirian, P / Baghurst, P A / Zatonski, W / Fontham, E / Bamlet, W R / Holly, E A / Bertuccio, P / Gao, Y T / Hassan, M / Yu, H / Kurtz, R C / Cotterchio, M / Su, J / Maisonneuve, P / Duell, E J / Boffetta, P / La Vecchia, C. ·Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. cristina.bosetti@marionegri.it ·Ann Oncol · Pubmed #22104574.

ABSTRACT: BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

18 Article Alcohol consumption and pancreatic cancer: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). 2012

Lucenteforte, E / La Vecchia, C / Silverman, D / Petersen, G M / Bracci, P M / Ji, B T / Bosetti, C / Li, D / Gallinger, S / Miller, A B / Bueno-de-Mesquita, H B / Talamini, R / Polesel, J / Ghadirian, P / Baghurst, P A / Zatonski, W / Fontham, E / Bamlet, W R / Holly, E A / Gao, Y T / Negri, E / Hassan, M / Cotterchio, M / Su, J / Maisonneuve, P / Boffetta, P / Duell, E J. ·Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri Milan, Milan, Italy. ·Ann Oncol · Pubmed #21536662.

ABSTRACT: BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.

19 Article Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4). 2011

Bertuccio, P / La Vecchia, C / Silverman, D T / Petersen, G M / Bracci, P M / Negri, E / Li, D / Risch, H A / Olson, S H / Gallinger, S / Miller, A B / Bueno-de-Mesquita, H B / Talamini, R / Polesel, J / Ghadirian, P / Baghurst, P A / Zatonski, W / Fontham, E T / Bamlet, W R / Holly, E A / Lucenteforte, E / Hassan, M / Yu, H / Kurtz, R C / Cotterchio, M / Su, J / Maisonneuve, P / Duell, E J / Bosetti, C / Boffetta, P. ·Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. ·Ann Oncol · Pubmed #21245160.

ABSTRACT: BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

20 Article Serum C-reactive protein and risk of pancreatic cancer in two nested, case-control studies. 2011

Douglas, Jason B / Silverman, Debra T / Weinstein, Stephanie J / Graubard, Barry I / Pollak, Michael N / Tao, Yuzhen / Virtamo, Jarmo / Albanes, Demetrius / Stolzenberg-Solomon, Rachael Z. ·Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, Maryland, USA. ·Cancer Epidemiol Biomarkers Prev · Pubmed #21173171.

ABSTRACT: BACKGROUND: Many epidemiologic studies have examined the association between C-reactive protein (CRP) and risk of cancer with inconsistent results. METHODS: We conducted two nested, case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) to test whether prediagnostic circulating CRP concentrations were associated with pancreatic adenocarcinoma. Between 1985 and 2004, 311 cases occurred in ATBC and between 1994 and 2006, 182 cases occurred in PLCO. Controls (n = 510 in ATBC, n = 374 in PLCO) were alive at the time the case was diagnosed and were matched by age, date of blood draw, sex, and race. We used conditional logistic regression adjusted for smoking to calculate OR and 95% CI for pancreatic cancer. RESULTS: CRP concentrations (ng/mL) tended to be inversely or not associated with pancreatic cancer risk in ATBC, PLCO, and combined analyses [per standardized quintile increase in CRP, continuous OR = 0.94 (95% CI, 0.89-0.99), OR = 0.99 (95% CI, 0.95-1.04), OR = 0.98 (95% CI, 0.95-1.01), respectively]. In combined analyses, we observed a significant interaction (P(interaction) = 0.02) such that inverse associations were suggestive in younger (OR = 0.95; 95% CI, 0.90-1.01), but not older, participants. CONCLUSION: Our results do not support the hypothesis that higher CRP concentrations are associated with incident pancreatic cancer. IMPACT: Our results highlight the importance of investigating more specific biomarkers for inflammation that may reflect the biological mechanisms underlying pancreatic cancer in prospective cohort studies.

21 Article Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. 2011

Li, Donghui / Tang, Hongwei / Hassan, Manal M / Holly, Elizabeth A / Bracci, Paige M / Silverman, Debra T. ·Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. dLi@mdanderson.org ·Cancer Causes Control · Pubmed #21104117.

ABSTRACT: Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case-control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5-2.1]. Risk estimates decreased with increasing years with diabetes (≤2 years OR = 2.9, 95% CI = 2.1-3.9; 3-5 years OR = 1.9, 95% CI = 1.3-2.6; 6-10 years OR = 1.6, 95% CI = 1.2-2.3; 11-15 years OR = 1.3, 95% CI = 0.9-2.0; > 15 years OR = 1.4, 95% CI = 1.0-2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6-3.7) and was restricted to insulin use of ≤3 years (OR = 2.4). Insulin use of >10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3-0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking.

22 Article Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. 2010

Douglas, Jason B / Silverman, Debra T / Pollak, Michael N / Tao, Yuzhen / Soliman, Amr S / Stolzenberg-Solomon, Rachael Z. ·Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, Maryland, USA. ·Cancer Epidemiol Biomarkers Prev · Pubmed #20699371.

ABSTRACT: BACKGROUND: Experimental evidence suggests that an overexpression of insulin-like growth factor (IGF)-I is implicated in human pancreatic tumors. Increased IGF-II and decreased IGF binding protein (IGFBP)-3 serum concentrations have been linked to a number of other cancers. METHODS: We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up of up to 11.7 years). Two controls (n = 374), who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex, and date of blood draw. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with the use of conditional logistic regression, adjusting for smoking. RESULTS: IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly associated with pancreatic cancer (highest compared with lowest quartile: OR, 1.58; 95% CI, 0.91-2.76; and P-trend = 0.25; OR, 0.86; 95% CI, 0.49-1.50; and P-trend = 0.31; and OR, 0.88; 95% CI, 0.51-1.51; and P-trend = 0.47, respectively). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels (highest compared with lowest quartile: OR, 1.54; 95% CI, 0.89-2.66; P-trend = 0.04). CONCLUSION: A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which may be a risk factor for pancreatic cancer. IMPACT: Our results highlight the importance of this biomarker for further investigation in large prospective cohort studies and pooled analysis with other prospective cohorts.

23 Article Dietary fatty acids and pancreatic cancer in the NIH-AARP diet and health study. 2009

Thiébaut, Anne C M / Jiao, Li / Silverman, Debra T / Cross, Amanda J / Thompson, Frances E / Subar, Amy F / Hollenbeck, Albert R / Schatzkin, Arthur / Stolzenberg-Solomon, Rachael Z. ·Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. ·J Natl Cancer Inst · Pubmed #19561318.

ABSTRACT: BACKGROUND: Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. METHODS: We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995-1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. RESULTS: Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; P(trend) = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; P(trend) < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; P(trend) = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; P(trend) < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). CONCLUSION: In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.

24 Article Alcohol use and risk of pancreatic cancer: the NIH-AARP Diet and Health Study. 2009

Jiao, Li / Silverman, Debra T / Schairer, Catherine / Thiébaut, Anne C M / Hollenbeck, Albert R / Leitzmann, Michael F / Schatzkin, Arthur / Stolzenberg-Solomon, Rachael Z. ·Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA. jiaol@mail.nih.gov ·Am J Epidemiol · Pubmed #19299403.

ABSTRACT: The epidemiologic evidence for the role of alcohol use in pancreatic cancer development is equivocal. The authors prospectively examined the relation between alcohol use and risk of pancreatic cancer among 470,681 participants who were aged 50-71 years in 1995-1996 in the US National Institutes of Health-AARP Diet and Health Study. The authors identified 1,149 eligible exocrine pancreatic cancer cases through December 2003. Multivariate Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals with the referent group being light drinkers (<1 drink/day). The relative risks of developing pancreatic cancer were 1.45 (95% confidence interval (CI): 1.17, 1.80; P(trend) = 0.002) for heavy total alcohol use (>or=3 drinks/day, approximately 40 g of alcohol/day) and 1.62 (95% CI: 1.24, 2.10; P(trend) = 0.001) for heavy liquor use, compared with the respective referent group. The increased risk with heavy total alcohol use was seen in never smokers (relative risk = 1.35, 95% CI: 0.79, 2.30) and participants who quit smoking 10 or more years ago before baseline (relative risk = 1.41, 95% CI: 1.01, 2.00). These findings suggest a moderately increased pancreatic cancer risk with heavy alcohol use, particularly liquor; however, residual confounding by cigarette smoking cannot be completely excluded.

25 Article Serum vitamin D and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian screening trial. 2009

Stolzenberg-Solomon, Rachael Z / Hayes, Richard B / Horst, Ron L / Anderson, Kristin E / Hollis, Bruce W / Silverman, Debra T. ·Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Nutritional Epidemiology Branch, National Cancer Institute, NIH, Rockville, Maryland 20852, USA. rs221z@nih.gov ·Cancer Res · Pubmed #19208842.

ABSTRACT: Experimental evidence suggests that vitamin D has anticarcinogenic properties; however, a nested case-control study conducted in a population of male Finnish smokers found that higher 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status as determined by the sun and diet, was associated with a significant 3-fold increased risk for pancreatic cancer. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic serum 25(OH)D concentrations were associated with pancreatic cancer risk. Between 1994 and 2006, 184 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n = 368) who were alive at the time the case was diagnosed were selected for each case and matched by age, race, sex, and calendar date of blood draw (to control for seasonal variation). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression, adjusting for smoking and body mass index. Vitamin D concentrations were not associated with pancreatic cancer overall (highest versus lowest quintile, >82.3 versus <45.9 nmol/L: OR, 1.45; 95% CI, 0.66-3.15; P trend = 0.49). However, positive associations were observed among subjects with low estimated annual residential solar UBV exposure, but not among those with moderate to high annual exposure (P interaction = 0.015). We did not confirm the previous strong positive association between 25(OH)D and pancreatic cancer; however, the increased risk among participants with low residential UVB exposure is similar.

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