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Ann Oncol. 2014 Oct;25(10):2065-72. doi: 10.1093/annonc/mdu276. Epub 2014 Jul 23.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

Author information

1
Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy cristina.bosetti@marionegri.it.
2
Department of Epidemiology, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy.
3
M.D. Anderson Cancer Center, University of Texas, Houston.
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda.
5
Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester.
6
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA.
7
Queensland Institute of Medical Research, Brisbane, Australia.
8
Department of Public Health Sciences, Penn State University, Penn State.
9
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, USA.
10
University Health Network, Department of Surgery, University of Toronto, Toronto, Canada.
11
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA.
12
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
13
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.
14
International Agency for Research on Cancer (IARC), Lyon, France.
15
Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc.
16
Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
17
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.
18
Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, Aviano.
19
Department of Preclinical and Clinical Pharmacology Mario Aiazzi Mancini, Università degli Studi di Firenze, Florence, Italy.
20
Regional Authority of Public Health in Banská Bystrica, Banská Bystrica, Slovakia.
21
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
22
Public Health, Women's and Children's Hospital, Adelaide, SA, Australia.
23
Cancer Center and Institute of Oncology, Warsaw, Poland.
24
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic.
25
Louisiana State University School of Public Health, New Orleans, USA.
26
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada Cancer Care Ontario, Toronto, Canada.
27
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
28
Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
29
Department of Epidemiology, Harvard School of Public Health, Boston, USA.
30
Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
31
The Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, USA.
32
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.

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.

KEYWORDS:

case–control study; diabetes; insulin; oral antidiabetics; pancreatic cancer; pooled analysis

PMID:
25057164
PMCID:
PMC4176453
DOI:
10.1093/annonc/mdu276
[Indexed for MEDLINE]
Free PMC Article

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