title: Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy. Electronic address: cristina.bosetti@marionegri.it.
authors: C
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authors: Bosetti
authors: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy.
authors: V
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authors: Rosato
authors: M.D. Anderson Cancer Center, University of Texas, Houston.
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authors: Li
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda.
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authors: Silverman
authors: Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester.
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authors: Petersen
authors: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA.
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authors: Queensland Institute of Medical Research, Brisbane, Australia.
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authors: Neale
authors: Department of Public Health Sciences, Penn State University, Penn State.
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authors: Muscat
authors: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA.
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authors: Anderson
authors: University Health Network, Department of Surgery, University of Toronto, Toronto, Canada.
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authors: Gallinger
authors: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.
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authors: Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
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authors: Miller
authors: 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.
authors: H
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authors: Bas Bueno-de-Mesquita
authors: International Agency for Research on Cancer (IARC), Lyon, France.
authors: G
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authors: Scelo
authors: Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc.
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authors: Janout
authors: Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
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authors: 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.
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authors: Lagiou
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano.
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authors: Serraino
authors: Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, Università degli Studi di Firenze, Florence, Italy.
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authors: Lucenteforte
authors: Regional Authority of Public Health in Banská Bystrica, Banská Bystrica, Slovakia.
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authors: Fabianova
authors: Public Health, Women's and Children's Hospital, Adelaide, SA, Australia.
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authors: Baghurst
authors: Cancer Center and Institute of Oncology, Warsaw, Poland.
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authors: Zatonski
authors: Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic.
authors: L
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authors: Foretova
authors: Louisiana State University School of Public Health, New Orleans, USA.
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authors: Fontham
authors: Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester.
authors: W R
authors: WR
authors: Bamlet
authors: Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA.
authors: E A
authors: EA
authors: Holly
authors: Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy.
authors: E
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authors: Negri
authors: M.D. Anderson Cancer Center, University of Texas, Houston.
authors: M
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authors: Hassan
authors: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA.
authors: A
authors: A
authors: Prizment
authors: Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; Cancer Care Ontario, Toronto, Canada.
authors: M
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authors: Cotterchio
authors: University Health Network, Department of Surgery, University of Toronto, Toronto, Canada.
authors: S
authors: S
authors: Cleary
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
authors: R C
authors: RC
authors: Kurtz
authors: Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
authors: P
authors: P
authors: Maisonneuve
authors: Department of Epidemiology, Harvard School of Public Health, Boston, USA.
authors: D
authors: D
authors: Trichopoulos
authors: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano.
authors: J
authors: J
authors: Polesel
authors: Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors: E J
authors: EJ
authors: Duell
authors: The Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors: P
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authors: Boffetta
authors: Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
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authors: La Vecchia
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authors: Ghadirian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D012907:Smoking
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: case–control study; diabetes; insulin; oral antidiabetics; pancreatic cancer; pooled analysis