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Pancreatic Neoplasms: HELP
Articles by Stephen K. Van Den Eeden
Based on 10 articles published since 2009
(Why 10 articles?)
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Between 2009 and 2019, Stephen K. Van Den Eeden wrote the following 10 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Diet-related inflammation and risk of prostate cancer in the California Men's Health Study. 2019

McMahon, Daria M / Burch, James B / Hébert, James R / Hardin, James W / Zhang, Jiajia / Wirth, Michael D / Youngstedt, Shawn D / Shivappa, Nitin / Jacobsen, Steven J / Caan, Bette / Van Den Eeden, Stephen K. ·Department of Epidemiology and Biostatistics, University of South Carolina, Columbia. · Department of Epidemiology and Biostatistics, University of South Carolina, Columbia; Cancer Prevention and Control Program, University of South Carolina, Columbia; WJB Dorn Department of Veterans Affairs Medical Center, Columbia, SC. · Department of Epidemiology and Biostatistics, University of South Carolina, Columbia; Cancer Prevention and Control Program, University of South Carolina, Columbia; Connecting Health Innovations, LLC, Columbia, SC. Electronic address: jhebert@sc.edu. · Department of Epidemiology and Biostatistics, University of South Carolina, Columbia; Cancer Prevention and Control Program, University of South Carolina, Columbia; Connecting Health Innovations, LLC, Columbia, SC. · College of Nursing and Health Innovation, Arizona State University, Phoenix; Phoenix VA Health Care System, Phoenix, AZ. · Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena. · Division of Research, Kaiser Permanente Northern California, Oakland. ·Ann Epidemiol · Pubmed #30503073.

ABSTRACT: PURPOSE: The purpose of the study was to examine the relationship between proinflammatory diet and prostate cancer risk. METHODS: Energy-adjusted Dietary Inflammatory Index (E-DII) scores were computed among 40,161 participants in the California Men's Health Study. Over 9.7 ± 3.8 years of follow-up, 2707 incident prostate cancer cases were diagnosed and categorized as low-, intermediate-, or high-risk, based on disease grade and stage. Accelerated failure-time models assessed time to diagnosis of prostate cancer. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (95% CI). Nonlinear effects of E-DII were modeled as third-order polynomials. RESULTS: Time to prostate cancer diagnosis did not differ by E-DII quartile. The HR for high-risk prostate cancer increased in the third E-DII quartile (HR CONCLUSIONS: Relationships between proinflammatory diet and prostate cancer risk may be nonlinear, with an increased risk above an E-DII threshold of ≈+2.5.

2 Article A Prospective Study to Establish a New-Onset Diabetes Cohort: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. 2018

Maitra, Anirban / Sharma, Ayush / Brand, Randall E / Van Den Eeden, Stephen K / Fisher, William E / Hart, Phil A / Hughes, Steven J / Mather, Kieren J / Pandol, Stephen J / Park, Walter G / Feng, Ziding / Serrano, Jose / Rinaudo, Jo Ann S / Srivastava, Sudhir / Chari, Suresh T / Anonymous601600. ·Division of Gastroenterology, Department of Medicine, Mayo Clinic, Rochester, MN. · Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA. · Division of Research, Kaiser Permanente Northern California, Oakland, CA. · Division of Gastroenterology, Baylor College of Medicine, Houston, TX. · Division of Gastroenterology, The Ohio State University Wexner Medical Center, Columbus, OH. · Department of Surgery, College of Medicine, University of Florida Health Science Center, Gainesville, FL. · Division of Endocrinology and Metabolism, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. · Division of Gastroenterology, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA. · Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA. · Department of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA. · Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. · Division of Cancer Prevention, National Cancer Institute, Rockville, MD. ·Pancreas · Pubmed #30325864.

ABSTRACT: The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are described in another article in this journal). One of the key objectives of CPDPC is to assemble a cohort of 10,000 subjects 50 years or older with new-onset diabetes, called the NOD cohort. Using a define, enrich, and find early detection approach, the aims of the NOD study are to (a) estimate the 3-year probability of pancreatic ductal adenocarcinoma (PDAC) in NOD (define), (b) establish a biobank of clinically annotated biospecimens from presymptomatic PDAC and control new-onset type 2 diabetes mellitus subjects, (c) conduct phase 3 validation studies of promising biomarkers for identification of incident PDAC in NOD patients (enrich), and (d) provide a platform for development of a future interventional screening protocol for early detection of PDAC in patients with NOD that incorporates imaging studies and/or clinical algorithms (find). It is expected that 85 to 100 incidences of PDAC will be diagnosed during the study period in this cohort of 10,000 patients.

3 Article PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. 2018

Yadav, Dhiraj / Park, Walter G / Fogel, Evan L / Li, Liang / Chari, Suresh T / Feng, Ziding / Fisher, William E / Forsmark, Christopher E / Jeon, Christie Y / Habtezion, Aida / Hart, Phil A / Hughes, Steven J / Othman, Mohamed O / Rinaudo, Jo Ann S / Pandol, Stephen J / Tirkes, Temel / Serrano, Jose / Srivastava, Sudhir / Van Den Eeden, Stephen K / Whitcomb, David C / Topazian, Mark / Conwell, Darwin L / Anonymous1531565. ·Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA. · Digestive and Liver Disorders, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. · Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. · Biostatistics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA. · Division of General Surgery, Baylor College of Medicine, Houston, TX. · Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL. · Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA. · Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH. · Department of Surgery, University of Florida, Gainesville, FL. · Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX. · Cancer Biomarker Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Rockville, MD. · Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA. · Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN. · Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. · Division of Research, Kaiser Permanente Northern California, Oakland, CA. ·Pancreas · Pubmed #30325862.

ABSTRACT: Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

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 Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. 2015

Lewis, James D / Habel, Laurel A / Quesenberry, Charles P / Strom, Brian L / Peng, Tiffany / Hedderson, Monique M / Ehrlich, Samantha F / Mamtani, Ronac / Bilker, Warren / Vaughn, David J / Nessel, Lisa / Van Den Eeden, Stephen K / Ferrara, Assiamira. ·Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania3Department of Medicine, University of Pennsylvania. · Division of Research, Kaiser Permanente Northern California, Oakland. · Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania5Rutgers Biomedical and Health Sciences, New Brunswick, New Jersey. · Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania. · Department of Medicine, University of Pennsylvania. · Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia. ·JAMA · Pubmed #26197187.

ABSTRACT: IMPORTANCE: Studies suggest pioglitazone use may increase risk of cancers. OBJECTIVE: To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. DESIGN, SETTING, AND PARTICIPANTS: Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California. EXPOSURES: Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent. MAIN OUTCOMES AND MEASURES: Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. RESULTS: Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose. CONCLUSIONS AND RELEVANCE: Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality.

6 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 / 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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.

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

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

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

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

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

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

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

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

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

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

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

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