Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Aug;80(11):1830–1837. doi: 10.1038/sj.bjc.6690607

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

D T Silverman 1, M Schiffman 1, J Everhart 2, A Goldstein 1, K D Lillemoe 3, G M Swanson 4,2, A G Schwartz 4,3, L M Brown 1, R S Greenberg 5,4, J B Schoenberg 6, L M Pottern 7, R N Hoover 1, J F Fraumeni Jr 1
PMCID: PMC2363127  PMID: 10468306

Abstract

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9–1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer. © 1999 Cancer Research Campaign

Keywords: diabetes mellitus, cholecystectomy, allergies, family history of cancer, pancreatic neoplasm

Full Text

The Full Text of this article is available as a PDF (116.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Breslow N. E., Day N. E. Statistical methods in cancer research. Volume I - The analysis of case-control studies. IARC Sci Publ. 1980;(32):5–338. [PubMed] [Google Scholar]
  2. Bueno de Mesquita H. B., Maisonneuve P., Moerman C. J., Walker A. M. Aspects of medical history and exocrine carcinoma of the pancreas: a population-based case-control study in The Netherlands. Int J Cancer. 1992 Aug 19;52(1):17–23. doi: 10.1002/ijc.2910520105. [DOI] [PubMed] [Google Scholar]
  3. Calle E. E., Murphy T. K., Rodriguez C., Thun M. J., Heath C. W., Jr Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control. 1998 Aug;9(4):403–410. doi: 10.1023/a:1008819701485. [DOI] [PubMed] [Google Scholar]
  4. Caygill C. P., Hill M. J., Hall C. N., Kirkham J. S., Northfield T. C. Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer. Gut. 1987 Aug;28(8):924–928. doi: 10.1136/gut.28.8.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chow W. H., Gridley G., Nyrén O., Linet M. S., Ekbom A., Fraumeni J. F., Jr, Adami H. O. Risk of pancreatic cancer following diabetes mellitus: a nationwide cohort study in Sweden. J Natl Cancer Inst. 1995 Jun 21;87(12):930–931. doi: 10.1093/jnci/87.12.930. [DOI] [PubMed] [Google Scholar]
  6. Colditz G. A., Willett W. C., Rotnitzky A., Manson J. E. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995 Apr 1;122(7):481–486. doi: 10.7326/0003-4819-122-7-199504010-00001. [DOI] [PubMed] [Google Scholar]
  7. Cuzick J., Babiker A. G. Pancreatic cancer, alcohol, diabetes mellitus and gall-bladder disease. Int J Cancer. 1989 Mar 15;43(3):415–421. doi: 10.1002/ijc.2910430312. [DOI] [PubMed] [Google Scholar]
  8. Dai Q., Zheng W., Ji B. T., Shu X. O., Jin F., Zhu J. L., Gao Y. T. Prior immunity-related medical conditions and pancreatic-cancer risk in Shanghai. Int J Cancer. 1995 Nov 3;63(3):337–340. doi: 10.1002/ijc.2910630305. [DOI] [PubMed] [Google Scholar]
  9. Eide T. J., Viste A., Andersen A., Søoreide O. The risk of cancer at all sites following gastric operation for benign disease. A cohort study of 4,224 patients. Int J Cancer. 1991 May 30;48(3):333–339. doi: 10.1002/ijc.2910480304. [DOI] [PubMed] [Google Scholar]
  10. Ekbom A., Yuen J., Karlsson B. M., McLaughlin J. K., Adami H. O. Risk of pancreatic and periampullar cancer following cholecystectomy: a population-based cohort study. Dig Dis Sci. 1996 Feb;41(2):387–391. doi: 10.1007/BF02093833. [DOI] [PubMed] [Google Scholar]
  11. Everhart J., Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 1995 May 24;273(20):1605–1609. [PubMed] [Google Scholar]
  12. Falk R. T., Pickle L. W., Fontham E. T., Correa P., Fraumeni J. F., Jr Life-style risk factors for pancreatic cancer in Louisiana: a case-control study. Am J Epidemiol. 1988 Aug;128(2):324–336. doi: 10.1093/oxfordjournals.aje.a114972. [DOI] [PubMed] [Google Scholar]
  13. Farrow D. C., Davis S. Risk of pancreatic cancer in relation to medical history and the use of tobacco, alcohol and coffee. Int J Cancer. 1990 May 15;45(5):816–820. doi: 10.1002/ijc.2910450504. [DOI] [PubMed] [Google Scholar]
  14. Fernandez E., La Vecchia C., D'Avanzo B., Negri E., Franceschi S. Family history and the risk of liver, gallbladder, and pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 1994 Apr-May;3(3):209–212. [PubMed] [Google Scholar]
  15. Fisher W. E., Boros L. G., Schirmer W. J. Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors. J Surg Res. 1996 Jun;63(1):310–313. doi: 10.1006/jsre.1996.0266. [DOI] [PubMed] [Google Scholar]
  16. Friedman G. D., van den Eeden S. K. Risk factors for pancreatic cancer: an exploratory study. Int J Epidemiol. 1993 Feb;22(1):30–37. doi: 10.1093/ije/22.1.30. [DOI] [PubMed] [Google Scholar]
  17. Gavaldà L., Porta M., Malats N., Piñol J. L., Fernández E., Maguire A., Cortès I., Carrillo E., Marrugat M., Rifà J. Concordancia entre la información facilitada por el paciente y un familiar sobre antecedentes patológicos, consumo de tabaco, de alcohol, de café, y dieta en el cáncer de páncreas exocrino y del sistema biliar extrahepático. Gac Sanit. 1995 Nov-Dec;9(51):334–342. doi: 10.1016/s0213-9111(95)71258-4. [DOI] [PubMed] [Google Scholar]
  18. Ghadirian P., Boyle P., Simard A., Baillargeon J., Maisonneuve P., Perret C. Reported family aggregation of pancreatic cancer within a population-based case-control study in the Francophone community in Montreal, Canada. Int J Pancreatol. 1991 Nov-Dec;10(3-4):183–196. doi: 10.1007/BF02924156. [DOI] [PubMed] [Google Scholar]
  19. Gold E. B., Gordis L., Diener M. D., Seltser R., Boitnott J. K., Bynum T. E., Hutcheon D. F. Diet and other risk factors for cancer of the pancreas. Cancer. 1985 Jan 15;55(2):460–467. doi: 10.1002/1097-0142(19850115)55:2<460::aid-cncr2820550229>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  20. Green A., Jensen O. M. Frequency of cancer among insulin-treated diabetic patients in Denmark. Diabetologia. 1985 Mar;28(3):128–130. doi: 10.1007/BF00273858. [DOI] [PubMed] [Google Scholar]
  21. Gullo L., Pezzilli R., Morselli-Labate A. M., Italian Pancreatic Cancer Study Group Risk of pancreatic cancer associated with cholelithiasis, cholecystectomy, or gastrectomy. Dig Dis Sci. 1996 Jun;41(6):1065–1068. doi: 10.1007/BF02088220. [DOI] [PubMed] [Google Scholar]
  22. Howatson A. G., Carter D. C. Pancreatic carcinogenesis-enhancement by cholecystokinin in the hamster-nitrosamine model. Br J Cancer. 1985 Jan;51(1):107–114. doi: 10.1038/bjc.1985.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hyvärinen H., Partanen S. Association of cholecystectomy with abdominal cancers. Hepatogastroenterology. 1987 Dec;34(6):280–284. [PubMed] [Google Scholar]
  24. Jain M., Howe G. R., St Louis P., Miller A. B. Coffee and alcohol as determinants of risk of pancreas cancer: a case-control study from Toronto. Int J Cancer. 1991 Feb 1;47(3):384–389. doi: 10.1002/ijc.2910470313. [DOI] [PubMed] [Google Scholar]
  25. Ji B. T., Hatch M. C., Chow W. H., McLaughlin J. K., Dai Q., Howe G. R., Gao Y. T., Fraumeni J. F., Jr Anthropometric and reproductive factors and the risk of pancreatic cancer: a case-control study in Shanghai, China. Int J Cancer. 1996 May 16;66(4):432–437. doi: 10.1002/(SICI)1097-0215(19960516)66:4<432::AID-IJC4>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  26. Johansen C., Chow W. H., Jørgensen T., Mellemkjaer L., Engholm G., Olsen J. H. Risk of colorectal cancer and other cancers in patients with gall stones. Gut. 1996 Sep;39(3):439–443. doi: 10.1136/gut.39.3.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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 Jul;4(4):375–382. doi: 10.1007/BF00051341. [DOI] [PubMed] [Google Scholar]
  28. Kazakoff K., Cardesa T., Liu J., Adrian T. E., Bagchi D., Bagchi M., Birt D. F., Pour P. M. Effects of voluntary physical exercise on high-fat diet-promoted pancreatic carcinogenesis in the hamster model. Nutr Cancer. 1996;26(3):265–279. doi: 10.1080/01635589609514483. [DOI] [PubMed] [Google Scholar]
  29. La Vecchia C., Negri E., D'Avanzo B., Ferraroni M., Gramenzi A., Savoldelli R., Boyle P., Franceschi S. Medical history, diet and pancreatic cancer. Oncology. 1990;47(6):463–466. doi: 10.1159/000226872. [DOI] [PubMed] [Google Scholar]
  30. Landis S. H., Murray T., Bolden S., Wingo P. A. Cancer statistics, 1998. CA Cancer J Clin. 1998 Jan-Feb;48(1):6–29. doi: 10.3322/canjclin.48.1.6. [DOI] [PubMed] [Google Scholar]
  31. Lin R. S., Kessler I. I. A multifactorial model for pancreatic cancer in man. Epidemiologic evidence. JAMA. 1981 Jan 9;245(2):147–152. [PubMed] [Google Scholar]
  32. Lumadue J. A., Griffin C. A., Osman M., Hruban R. H. Familial pancreatic cancer and the genetics of pancreatic cancer. Surg Clin North Am. 1995 Oct;75(5):845–855. doi: 10.1016/s0039-6109(16)46731-9. [DOI] [PubMed] [Google Scholar]
  33. Lynch H. T., Voorhees G. J., Lanspa S. J., McGreevy P. S., Lynch J. F. Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. Br J Cancer. 1985 Aug;52(2):271–273. doi: 10.1038/bjc.1985.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mack T. M., Yu M. C., Hanisch R., Henderson B. E. Pancreas cancer and smoking, beverage consumption, and past medical history. J Natl Cancer Inst. 1986 Jan;76(1):49–60. [PubMed] [Google Scholar]
  35. Maringhini A., Thiruvengadam R., Melton L. J., 3rd, Hench V. S., Zinsmeister A. R., DiMagno E. P. Pancreatic cancer risk following gastric surgery. Cancer. 1987 Jul 15;60(2):245–247. doi: 10.1002/1097-0142(19870715)60:2<245::aid-cncr2820600222>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  36. McLaughlin J. K., Mandel J. S., Mehl E. S., Blot W. J. Comparison of next-of-kin with self-respondents regarding questions on cigarette, coffee, and alcohol consumption. Epidemiology. 1990 Sep;1(5):408–412. doi: 10.1097/00001648-199009000-00013. [DOI] [PubMed] [Google Scholar]
  37. Micozzi M. S., Albanes D., Jones D. Y., Chumlea W. C. Correlations of body mass indices with weight, stature, and body composition in men and women in NHANES I and II. Am J Clin Nutr. 1986 Dec;44(6):725–731. doi: 10.1093/ajcn/44.6.725. [DOI] [PubMed] [Google Scholar]
  38. Mills P. K., Beeson W. L., Abbey D. E., Fraser G. E., Phillips R. L. Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists. Cancer. 1988 Jun 15;61(12):2578–2585. doi: 10.1002/1097-0142(19880615)61:12<2578::aid-cncr2820611232>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  39. Møller H., Mellemgaard A., Lindvig K., Olsen J. H. Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer. 1994;30A(3):344–350. doi: 10.1016/0959-8049(94)90254-2. [DOI] [PubMed] [Google Scholar]
  40. Møller H., Toftgaard C. Cancer occurrence in a cohort of patients surgically treated for peptic ulcer. Gut. 1991 Jul;32(7):740–744. doi: 10.1136/gut.32.7.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Norell S., Ahlbom A., Erwald R., Jacobson G., Lindberg-Navier I., Olin R., Wiechel K. L. Diabetes, gall stone disease, and pancreatic cancer. Br J Cancer. 1986 Aug;54(2):377–378. doi: 10.1038/bjc.1986.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Offerhaus G. J., Giardiello F. M., Moore G. W., Tersmette A. C. Partial gastrectomy: a risk factor for carcinoma of the pancreas? Hum Pathol. 1987 Mar;18(3):285–288. doi: 10.1016/s0046-8177(87)80011-4. [DOI] [PubMed] [Google Scholar]
  43. Permert J., Larsson J., Westermark G. T., Herrington M. K., Christmanson L., Pour P. M., Westermark P., Adrian T. E. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med. 1994 Feb 3;330(5):313–318. doi: 10.1056/NEJM199402033300503. [DOI] [PubMed] [Google Scholar]
  44. Pour P. M., Kazakoff K. Stimulation of islet cell proliferation enhances pancreatic ductal carcinogenesis in the hamster model. Am J Pathol. 1996 Sep;149(3):1017–1025. [PMC free article] [PubMed] [Google Scholar]
  45. Ross A. H., Smith M. A., Anderson J. R., Small W. P. Late mortality after surgery for peptic ulcer. N Engl J Med. 1982 Aug 26;307(9):519–522. doi: 10.1056/NEJM198208263070902. [DOI] [PubMed] [Google Scholar]
  46. Shibata A., Mack T. M., Paganini-Hill A., Ross R. K., Henderson B. E. A prospective study of pancreatic cancer in the elderly. Int J Cancer. 1994 Jul 1;58(1):46–49. doi: 10.1002/ijc.2910580109. [DOI] [PubMed] [Google Scholar]
  47. Silverman D. T., Brown L. M., Hoover R. N., Schiffman M., Lillemoe K. D., Schoenberg J. B., Swanson G. M., Hayes R. B., Greenberg R. S., Benichou J. Alcohol and pancreatic cancer in blacks and whites in the United States. Cancer Res. 1995 Nov 1;55(21):4899–4905. [PubMed] [Google Scholar]
  48. Silverman D. T., Dunn J. A., Hoover R. N., Schiffman M., Lillemoe K. D., Schoenberg J. B., Brown L. M., Greenberg R. S., Hayes R. B., Swanson G. M. Cigarette smoking and pancreas cancer: a case-control study based on direct interviews. J Natl Cancer Inst. 1994 Oct 19;86(20):1510–1516. doi: 10.1093/jnci/86.20.1510. [DOI] [PubMed] [Google Scholar]
  49. Silverman D. T., Schiffman M., Devesa S. Diagnostic certainty in pancreatic cancer. J Clin Epidemiol. 1996 May;49(5):601–603. doi: 10.1016/0895-4356(95)00508-0. [DOI] [PubMed] [Google Scholar]
  50. Silverman D. T., Swanson C. A., Gridley G., Wacholder S., Greenberg R. S., Brown L. M., Hayes R. B., Swanson G. M., Schoenberg J. B., Pottern L. M. Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst. 1998 Nov 18;90(22):1710–1719. doi: 10.1093/jnci/90.22.1710. [DOI] [PubMed] [Google Scholar]
  51. Smith J. P., Solomon T. E., Bagheri S., Kramer S. Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990. Dig Dis Sci. 1990 Nov;35(11):1377–1384. doi: 10.1007/BF01536744. [DOI] [PubMed] [Google Scholar]
  52. Tersmette A. C., Offerhaus G. J., Giardiello F. M., Tersmette K. W., Vandenbroucke J. P., Tytgat G. N. Occurrence of non-gastric cancer in the digestive tract after remote partial gastrectomy: analysis of an Amsterdam cohort. Int J Cancer. 1990 Nov 15;46(5):792–795. doi: 10.1002/ijc.2910460507. [DOI] [PubMed] [Google Scholar]
  53. Warshaw A. L., Fernández-del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992 Feb 13;326(7):455–465. doi: 10.1056/NEJM199202133260706. [DOI] [PubMed] [Google Scholar]
  54. Wideroff L., Gridley G., Mellemkjaer L., Chow W. H., Linet M., Keehn S., Borch-Johnsen K., Olsen J. H. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst. 1997 Sep 17;89(18):1360–1365. doi: 10.1093/jnci/89.18.1360. [DOI] [PubMed] [Google Scholar]
  55. Wynder E. L., Mabuchi K., Maruchi N., Fortner J. G. Epidemiology of cancer of the pancreas. J Natl Cancer Inst. 1973 Mar;50(3):645–667. doi: 10.1093/jnci/50.3.645. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES