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, Joshua 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. Fabianova & 19 others P. 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 journalArticle

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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

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Bosetti, C. ; Rosato, V. ; Li, D. ; Silverman, D. ; Petersen, G. M. ; Bracci, P. M. ; Neale, R. E. ; Muscat, Joshua ; 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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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.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.",
author = "C. Bosetti and V. Rosato and D. Li and D. Silverman and Petersen, {G. M.} and Bracci, {P. M.} and Neale, {R. E.} and Joshua 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.",
year = "2014",
month = "10",
day = "1",
doi = "10.1093/annonc/mdu276",
language = "English (US)",
volume = "25",
pages = "2065--2072",
journal = "Annals of Oncology",
issn = "0923-7534",
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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

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, G. M.; Bracci, P. M.; Neale, R. E.; Muscat, Joshua; 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

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, G. M.

AU - Bracci, P. M.

AU - Neale, R. E.

AU - Muscat, Joshua

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.

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U2 - 10.1093/annonc/mdu276

DO - 10.1093/annonc/mdu276

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VL - 25

SP - 2065

EP - 2072

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 10

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