Cancer Causes & Control

, Volume 9, Issue 4, pp 403–410 | Cite as

Diabetes mellitus and pancreaticcancer mortality in a prospectivecohort of United States adults

  • Eugenia E. Calle
  • Terrell K. Murphy
  • Carmen Rodriguez
  • Michael J. Thun
  • Clark W. HeathJr.


Objectives: Diabetes mellitus and pancreatic cancer are known to be associated, but it is not known whether diabetes is a true risk factor, preceding development of the cancer, or if it is an early manifestation of the cancer. To address this uncertainty, we examined the association of pancreatic cancer mortality and reported diabetes of at least one year's duration in a large, prospective study of United States adults. The vast majority of diabetes in this cohort is likely to be non-insulin-dependent diabetes.

Methods: After 12 years of follow-up, 2,953 deaths from pancreatic cancer were observed in a cohort of 1,089,586 men and women who were cancer-free at study entry in 1982. Cox proportional hazards models, adjusted for age, race, smoking, family history of pancreatic cancer, body mass index (wt/ht2), and education, were used to assess associations.

Results: A history of diabetes was significantly related to pancreatic cancer mortality in both men (rate ratio [RR]=1.49, 95 percent confidence interval [CI]=1.25-1.77) and women (RR=1.51, CI=1.24-1.85). However, the strength of the association varied over the follow-up period. The death rate from pancreatic cancer was twice as high in diabetics as in non-diabetics during the second and third years of follow-up (adjusted RR=2.05, CI=1.56-2.69) but only about 40 percent higher in years nine to 12 (adjusted RR=1.38, CI=1.08-1.77).

Conclusions: The small but persistent increased risk of death from pancreatic cancer, seen even when the diagnosis of diabetes preceded death by many years, supports the hypothesis that diabetes may be a true, albeit modest, risk factor for pancreatic cancer.

Cohort studies diabetes mellitus pancreatic cancer risk factors United States 


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  1. 1.
    Adami HO, McLaughlin J, Ekbom A, et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control 1991; 2: 307–14.Google Scholar
  2. 2.
    Balkau B, Barrett-Connor E, Eschwege E, Richard JL, Claude JR, Ducimetiere P. Diabetes and pancreatic carcinoma. Diabetes Metab 1993; 19: 458–62.Google Scholar
  3. 3.
    Chow WH, Gridley G, Nyrén O, et al. Risk of pancreatic cancer following diabetes mellitus: a nationalwide cohort study in Sweden. J Natl Cancer Inst 1995; 87: 930–1.Google Scholar
  4. 4.
    Cuzick J, Babiker AG. Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease. Int J Cancer 1989; 43: 415–21.Google Scholar
  5. 5.
    Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer: a meta-analysis. JAMA 1995; 273: 1605–9.Google Scholar
  6. 6.
    Farrow DC, Davis S. Risk of pancreatic cancer in relation to medical history and the use of tobacco, alcohol and coffee. Int J Cancer 1990; 45: 816–20.Google Scholar
  7. 7.
    Friedman GD, Van den Eeden SK. Risk factors for pancreatic cancer: an exploratory study. Int J Epidemiol 1993; 22: 30–7.Google Scholar
  8. 8.
    Gullo L, Pezzilli R, Morselli-Labate AM, and the Italian Pancreatic Cancer Study Group. Diabetes and the risk of pancreatic cancer. N Engl J Med 1994; 331: 81–4.Google Scholar
  9. 9.
    Hiatt RA, Klatsky AL, Armstrong MA. Pancreatic cancer, blood glucose and beverage consumption. Int J Cancer 1988; 41: 794–7.Google Scholar
  10. 10.
    Jain M, Howe GR, St. Louis P, Miller AB. Coffee and alcohol as determinants of risk of pancreas cancer: a case control study from Toronto. Int J Cancer 1991; 47: 384–9.Google Scholar
  11. 11.
    Kalapothaki V, Tzonou A, Hsieh C-c, Toupadaki N, Karakatsani A, Trichopoulos D. Tobacco, ethanol, coffee, pancreatitis, diabetes mellitus, and cholelithiasis as risk factors for pancreatic carcinoma. Cancer Causes Control 1993; 4: 375–82.Google Scholar
  12. 12.
    Kessler II. Cancer mortality among diabetics. J Natl Cancer Inst 1970; 44: 673–86.Google Scholar
  13. 13.
    La Vecchia C, Negri E, D’Avanzo B, et al. Medical history, diet and pancreatic cancer. Oncology 1990; 47: 463–6.Google Scholar
  14. 14.
    La Vecchia C, Negri E, Franceschi S, D’Avanzo B, Boyle P. A case-control study of diabetes mellitus and cancer risk. Br J Cancer 1994; 70: 950–3.Google Scholar
  15. 15.
    Mills PK, Beeson WL, Abbey DE, Fraser GE, Phillips RL. Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists. Cancer 1988; 61: 2578–85.Google Scholar
  16. 16.
    Morris DV, Nabarro JDN. Pancreatic cancer and diabetes mellitus. Diabetic Med 1984; 1: 119–21.Google Scholar
  17. 17.
    Norell S, Ahlbom A. Diabetes, gall stone disease, and pancreatic cancer [Letter]. Br J Cancer 1986; 54: 377–8.Google Scholar
  18. 18.
    Ragozzino M, Melton LJ III, Chu CP, Palumbo PJ. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chron Dis 1982; 35: 13–9.Google Scholar
  19. 19.
    Whittemore AS, Paffenbarger RS Jr, Anderson K, Halpern J. Early precursors of pancreatic cancer in college men. J Chron Dis 1983; 36: 251–6.Google Scholar
  20. 20.
    Wynder EL, Mabuchi K, Maruchi N, Fortner JG. Epidemiology of cancer of the pancreas. J Natl Cancer Inst 1973; 50: 645–67.Google Scholar
  21. 21.
    Davey-Smith G, Egger M, Shipley MJ, Marmot MG. Postchallenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. Am J Epidemiol 1992; 136: 1110–4.Google Scholar
  22. 22.
    Permert J, Ihse I, Jorfeldt L, von Schenck H, Arngvist HJ, Larsson J. Pancreatic cancer is associated with impaired glucose metabolism. Eur J Surg 1993; 159: 101–7.Google Scholar
  23. 23.
    Noy A, Bilezikian JP. Clinical review 63, diabetes and pancreatic cancer: clues to the early diagnosis of pancreatic malignancy. J Clin Endocrinol Metab 1994; 79: 1223–31.Google Scholar
  24. 24.
    Permert J, Ihse I, Jorfeldt L, von Schenck H, Arngvist HJ, Larsson J. Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer. Br J Surg 1993; 80: 1047–50.Google Scholar
  25. 25.
    Warshaw AL, Fernández-del Castillo C. Pancreatic carcinoma. N Engl J Med 1992; 326: 455–65.Google Scholar
  26. 26.
    Garfinkel L. Selection, follow-up, and analysis in the American Cancer Society prospective studies. Mongr Natl Cancer Inst 1985; 67: 49–52.Google Scholar
  27. 27.
    Stellman SD, Garfinkel L. Smoking habits and tar levels in a new American Cancer Society prospective study of 1.2 million men and women. J Natl Cancer Inst 1986; 76: 1057–63.Google Scholar
  28. 28.
    Calle EE, Terrell DD. Utility of the National Death Index for ascertainment of mortality among Cancer Prevention Study II participants. Am J Epidemiol 1993; 137: 235–41Google Scholar
  29. 29.
    World Health Organization. International Classification of Diseases. Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death. Vol. 1. Ninth Revision. Geneva, Switzerland: World Health Organization, 1977.Google Scholar
  30. 30.
    Rothman KJ. Modern Epidemiology. Boston, MA (USA): Little, Brown, 1986.Google Scholar
  31. 31.
    Flanders WD. Approximate variance formulas for standardized rate ratios. J Chronic Dis 1984; 37: 449–53.Google Scholar
  32. 32.
    Cox DR. Regression models and life tables (with discussion). J R Stat Soc (B) 1972; 34: 187–220.Google Scholar
  33. 33.
    Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic Research: Principles and Quantatitive Methods. New York, NY (USA): Van Nostrad Reinhold Company, 1982.Google Scholar
  34. 34.
    Fisher WE, McCullough PJ, Ray MB, Rogers DH, Bell RH Jr. Diabetes enhances growth of pancreatic carcinoma cells. Surgery 1988; 104: 431–6.Google Scholar
  35. 35.
    Fisher WE, McCullough PJ, Ramo OJ, Bell RH Jr. Further studies of enhanced growth of pancreatic carcinoma in diabetes. J Surg Res 1996; 63: 310–3.Google Scholar
  36. 36.
    Fisher WE, Boros LG, Schirmer WJ. Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic terms. J Surg Res 1996; 63: 310–3.Google Scholar
  37. 37.
    Harlow SD, Linet MS. Argument between questionnaire data and medical records: evidence for accuracy of recall. Am J Epidemiol 1989; 129: 233–48.Google Scholar
  38. 38.
    Bush TL, Miller SR, Golden AL, Hale WE. Self-report and medical record report agreement of selected medical conditions in the elderly. Am J Public Health 1989; 79: 1554–6.Google Scholar
  39. 39.
    Harris MI, Hadden WC, Knowler WC, Bennett PH. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20-74 yr. Diabetes 1987; 36: 523–34.Google Scholar
  40. 40.
    Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 years before clinical diagnosis. Diabetes Care 1992; 15: 815–9.Google Scholar
  41. 41.
    Martin BC, Warram JH, Krowlewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 1992; 340: 925–9.Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Eugenia E. Calle
    • 1
  • Terrell K. Murphy
    • 1
  • Carmen Rodriguez
    • 1
  • Michael J. Thun
    • 1
  • Clark W. HeathJr.
    • 1
  1. 1.Department of Epidemiology and Surveillance ResearchAmerican Cancer SocietyAtlantaUSA

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