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

C. Bosetti, V. Rosato, D. Li, D. Silverman, G. M. Petersen, P. M. Bracci, R. E. Neale, J. Muscat, K. Anderson, S. Gallinger, S. H. Olson, A. B. Miller, H. Bas Bueno-de-Mesquita, G. Scelo, V. Janout, I. Holcatova, P. Lagiou, D. Serraino, E. Lucenteforte, E. FabianovaP. Ghadirian, P. A. Baghurst, W. Zatonski, L. Foretova, E. Fontham, W. R. Bamlet, E. A. Holly, E. Negri, M. Hassan, A. Prizment, M. Cotterchio, S. Cleary, R. C. Kurtz, P. Maisonneuve, D. Trichopoulos, J. Polesel, E. J. Duell, P. Boffetta, C. La Vecchia

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2065-2072
Number of pages8
JournalAnnals of Oncology
Volume25
Issue number10
DOIs
StatePublished - Oct 2014

Bibliographical note

Funding Information:
This work was conducted with the contribution of the Italian Association for Cancer Research (AIRC , project N. 13203, PI CB) and within the COST Action (BM1214) EU-Pancreas . The Central Europe study was supported by the Grant Agency of Ministry of Health of the Czech Republic ( IGA MZ ČR 8090-3 and 9422-3 ). The center of Brno, Czech Republic—within the Central Europe study—was supported by MH CZ—DRO ( MMCI, 00209805 ) and RECAMO CZ.1.05/2.1.00/03.0101 . The Italy and Milan studies were supported by the Italian Association for Cancer Research. The Louisiana State University study was supported by the Louisiana Board of Regents Millennium Trust Health Excellence Fund (Project 5: HEF 2000-05, Genetics Studies in the Acadian Population). The Mayo Clinic Biospecimen Resource for Pancreas Research is partially supported by The National Institutes of Health (NIH) US ( P50 CA102701 ). The MD Anderson Cancer Center study was supported by the NIH Research Project Grant Program ( RO1 CA98380 ). The Pancreatic Cancer Family Registry at the Memorial Sloan Kettering Cancer Center (MSKCC) was supported by the Prevention, Control, and Population Research Goldstein Award; the Society of MSKCC ; and the Geoffrey Beene Cancer Research Fund . The NCI study was supported by the Intramural Research Program of the National Institute of Health , National Cancer Institute, Division of Cancer Epidemiology and Genetics (contract numbers: N01-CP-51090 , N01-CP-51089 , N01-CP-51092 , N01-CP-05225 , N01-CP-31022 , and N01-CP-05227 ). The Penn State study was supported by the National Institutes of Health (NIH) US ( P01CA068384 ). The Queensland Pancreatic Cancer study was funded by the National Health and Medical Research Council (Australia) (grant 442302). The Montreal investigation in the Surveillance of Environmental Aspects Related to Cancer in Humans study was supported by the Cancer Research Society , the Toronto contribution was supported by the National Cancer Institute of Canada, and the Netherlands contribution was supported by the Dutch Ministry of Public Health, Welfare and Sports (formerly Welfare, Health and Culture). The Ontario Pancreas Cancer Study was supported by grants from the National Institutes of Health ( R01 CA97075 , as part of the PACGENE consortium and U01-CA74783 ), the Lustgarten Foundation for Pancreatic Cancer Research, and the Ontario Cancer Research Network . The University of California, San Francisco (UCSF) study work was supported in part by National Cancer Institute grants ( CA59706 , CA108370 , CA109767 , CA89726 , and CA098889) , and by the Rombauer Pancreatic Cancer Research Fund . Cancer incidence data collection in the UCSF study was supported by the California Department of Public Health, the National Cancer Institute's Surveillance, Epidemiology and End Results Program (contract N01-PC-35136) awarded to the Northern California Cancer Center. EJD was supported by the Red Temática de Investigación Cooperativa en Cáncer (RTICC; Rd06/0020/0091 and Rd12/0036/0018 ) and by the Generalitat de Catalunya. REN was funded by a National Health and Medical Research Council (Australia) Senior Research Fellowship .

Funding Information:
The authors thank Mrs Ivana Garimoldi for editorial assistance. This work was conducted with the contribution of the Italian Association for Cancer Research (AIRC, project N. 13203, PI CB) and within the COST Action (BM1214) EU-Pancreas. The Central Europe study was supported by the Grant Agency of Ministry of Health of the Czech Republic (IGA MZ ?R 8090-3 and 9422-3). The center of Brno, Czech Republic?within the Central Europe study?was supported by MH CZ?DRO (MMCI, 00209805) and RECAMO CZ.1.05/2.1.00/03.0101. The Italy and Milan studies were supported by the Italian Association for Cancer Research. The Louisiana State University study was supported by the Louisiana Board of Regents Millennium Trust Health Excellence Fund (Project 5: HEF 2000-05, Genetics Studies in the Acadian Population). The Mayo Clinic Biospecimen Resource for Pancreas Research is partially supported by The National Institutes of Health (NIH) US (P50 CA102701). The MD Anderson Cancer Center study was supported by the NIH Research Project Grant Program (RO1 CA98380). The Pancreatic Cancer Family Registry at the Memorial Sloan Kettering Cancer Center (MSKCC) was supported by the Prevention, Control, and Population Research Goldstein Award; the Society of MSKCC; and the Geoffrey Beene Cancer Research Fund. The NCI study was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (contract numbers: N01-CP-51090, N01-CP-51089, N01-CP-51092, N01-CP-05225, N01-CP-31022, and N01-CP-05227). The Penn State study was supported by the National Institutes of Health (NIH) US (P01CA068384). The Queensland Pancreatic Cancer study was funded by the National Health and Medical Research Council (Australia) (grant 442302). The Montreal investigation in the Surveillance of Environmental Aspects Related to Cancer in Humans study was supported by the Cancer Research Society, the Toronto contribution was supported by the National Cancer Institute of Canada, and the Netherlands contribution was supported by the Dutch Ministry of Public Health, Welfare and Sports (formerly Welfare, Health and Culture). The Ontario Pancreas Cancer Study was supported by grants from the National Institutes of Health (R01 CA97075, as part of the PACGENE consortium and U01-CA74783), the Lustgarten Foundation for Pancreatic Cancer Research, and the Ontario Cancer Research Network. The University of California, San Francisco (UCSF) study work was supported in part by National Cancer Institute grants (CA59706, CA108370, CA109767, CA89726, and CA098889), and by the Rombauer Pancreatic Cancer Research Fund. Cancer incidence data collection in the UCSF study was supported by the California Department of Public Health, the National Cancer Institute's Surveillance,Epidemiology and End Results Program (contract N01-PC-35136) awarded to the Northern California Cancer Center. EJD was supported by the Red Tem?tica de Investigaci?n Cooperativa en C?ncer (RTICC;Rd06/0020/0091 and Rd12/0036/0018) and by the Generalitat de Catalunya. REN was funded by a National Health and Medical Research Council (Australia) Senior Research Fellowship. The authors have declared no conflicts of interest.

Publisher Copyright:
© 2014 European Society for Medical Oncology

Keywords

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

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