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, Gloria 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

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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 : official journal of the European Society for Medical Oncology / ESMO
Volume25
Issue number10
DOIs
StatePublished - Oct 1 2014

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Pancreatic Neoplasms
Hypoglycemic Agents
Odds Ratio
Type 2 Diabetes Mellitus
Logistic Models
Insulin
Case-Control Studies
Body Mass Index
Smoking
Confidence Intervals
Interviews

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Diabetes, antidiabetic medications, and pancreatic cancer risk : an analysis from the International Pancreatic Cancer Case-Control Consortium. / Bosetti, C.; Rosato, V.; Li, D.; Silverman, D.; Petersen, Gloria 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.

In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, Vol. 25, No. 10, 01.10.2014, p. 2065-2072.

Research output: Contribution to journalArticle

Bosetti, C, Rosato, V, Li, D, Silverman, D, Petersen, GM, Bracci, PM, Neale, RE, Muscat, J, Anderson, K, Gallinger, S, Olson, SH, Miller, AB, Bas Bueno-de-Mesquita, H, Scelo, G, Janout, V, Holcatova, I, Lagiou, P, Serraino, D, Lucenteforte, E, Fabianova, E, Ghadirian, P, Baghurst, PA, Zatonski, W, Foretova, L, Fontham, E, Bamlet, WR, Holly, EA, Negri, E, Hassan, M, Prizment, A, Cotterchio, M, Cleary, S, Kurtz, RC, Maisonneuve, P, Trichopoulos, D, Polesel, J, Duell, EJ, Boffetta, P & La Vecchia, C 2014, 'Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium', Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, vol. 25, no. 10, pp. 2065-2072. https://doi.org/10.1093/annonc/mdu276
Bosetti, C. ; Rosato, V. ; Li, D. ; Silverman, D. ; Petersen, Gloria 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. / Diabetes, antidiabetic medications, and pancreatic cancer risk : an analysis from the International Pancreatic Cancer Case-Control Consortium. In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2014 ; Vol. 25, No. 10. pp. 2065-2072.
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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.",
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author = "C. Bosetti and V. Rosato and D. Li and D. Silverman and Petersen, {Gloria M} and Bracci, {P. M.} and Neale, {R. E.} and J. Muscat and K. Anderson and S. Gallinger and Olson, {S. H.} and Miller, {A. B.} and {Bas Bueno-de-Mesquita}, H. and G. Scelo and V. Janout and I. Holcatova and P. Lagiou and D. Serraino and E. Lucenteforte and E. Fabianova and P. Ghadirian and Baghurst, {P. A.} and W. Zatonski and L. Foretova and E. Fontham and Bamlet, {W. R.} and Holly, {E. A.} and E. Negri and M. Hassan and A. Prizment and M. Cotterchio and S. Cleary and Kurtz, {R. C.} and P. Maisonneuve and D. Trichopoulos and J. Polesel and Duell, {E. J.} and P. Boffetta and {La Vecchia}, C.",
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TY - JOUR

T1 - Diabetes, antidiabetic medications, and pancreatic cancer risk

T2 - an analysis from the International Pancreatic Cancer Case-Control Consortium

AU - Bosetti, C.

AU - Rosato, V.

AU - Li, D.

AU - Silverman, D.

AU - Petersen, Gloria M

AU - Bracci, P. M.

AU - Neale, R. E.

AU - Muscat, J.

AU - Anderson, K.

AU - Gallinger, S.

AU - Olson, S. H.

AU - Miller, A. B.

AU - Bas Bueno-de-Mesquita, H.

AU - Scelo, G.

AU - Janout, V.

AU - Holcatova, I.

AU - Lagiou, P.

AU - Serraino, D.

AU - Lucenteforte, E.

AU - Fabianova, E.

AU - Ghadirian, P.

AU - Baghurst, P. A.

AU - Zatonski, W.

AU - Foretova, L.

AU - Fontham, E.

AU - Bamlet, W. R.

AU - Holly, E. A.

AU - Negri, E.

AU - Hassan, M.

AU - Prizment, A.

AU - Cotterchio, M.

AU - Cleary, S.

AU - Kurtz, R. C.

AU - Maisonneuve, P.

AU - Trichopoulos, D.

AU - Polesel, J.

AU - Duell, E. J.

AU - Boffetta, P.

AU - La Vecchia, C.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

KW - case–control study

KW - diabetes

KW - insulin

KW - oral antidiabetics

KW - pancreatic cancer

KW - pooled analysis

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DO - 10.1093/annonc/mdu276

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