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Risk factors and early signs of pancreatic cancer in diabetes: screening strategy based on diabetes onset age

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background

Diabetes mellitus (DM) has long been recognized as a risk factor for pancreatic cancer (PaC) and recently has attracted attention as a manifestation of PaC. Diabetes is expected to be a clue for the early detection of PaC; however, no effective screening strategy has been established.

Methods

Forty diabetic patients with PaC were identified and compared with 120 diabetic patients without any malignancies. We analyzed risk factors for and early signs of PaC, focusing on the DM-onset age.

Results

As there were peaks at 40–45 years and 60–65 years in the distribution of DM-onset age, we analyzed the clinical characteristics of and risk factors for PaC according to DM-onset age: i.e., early-onset (<55 years) and late-onset (≥55 years). PaC was diagnosed within 2 years of DM onset (new-onset) in 0 % of the patients with early-onset DM, and in 33 % of those with late-onset DM. The mean duration of DM in patients with early-onset DM with PaC was longer than that in the late-onset patients (26 vs. 9 years; P < 0.01). A family history of DM (odds ratio [OR] 3.60) and use of insulin (OR 3.52) were significant risk factors in patients with early-onset DM, while the onset age of DM (OR 1.12) and multiple diabetic patients in the family (OR 6.13) were risk factors in those with late-onset DM. Body weight loss and exacerbation of DM were seen 12 months prior to PaC diagnosis in both groups.

Conclusions

Our study revealed specific risk factors for and similar early signs of PaC in early-onset and late-onset DM. Thus, we could develop a screening strategy, combining these risk factors specific for DM-onset age with early signs of disease.

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References

  1. Ministry of Health, Labour and Welfare. Vital Statistics Japan. 2008.

  2. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43–66.

    Article  PubMed  Google Scholar 

  3. DiMagno EP, Reber HA, Tempero MA. AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. American Gastroenterological Association. Gastroenterology. 1999;117:1464–84.

    Article  PubMed  CAS  Google Scholar 

  4. Huxley R, Ansary-Moghaddam A. Berrington de Gonzalez A, Barzi F and Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005;92:2076–83.

    Article  PubMed  CAS  Google Scholar 

  5. Lin Y, Kikuchi S, Tamakoshi A, Yagyu K, Obata Y, Inaba Y, et al. Obesity, physical activity and the risk of pancreatic cancer in a large Japanese cohort. Int J Cancer. 2007;120:2665–71.

    Article  PubMed  CAS  Google Scholar 

  6. Larsson SC, Orsini N, Wolk A. Body mass index and pancreatic cancer risk: a meta-analysis of prospective studies. Int J Cancer. 2007;120:1993–8.

    Article  PubMed  CAS  Google Scholar 

  7. Tada M, Kawabe T, Arizumi M, Togawa O, Matsubara S, Yamamoto N, et al. Pancreatic cancer in patients with pancreatic cystic lesions: a prospective study in 197 patients. Clin Gastroenterol Hepatol. 2006;4:1265–70.

    Article  PubMed  Google Scholar 

  8. Uehara H, Nakaizumi A, Ishikawa O, Iishi H, Tatsumi K, Takakura R, et al. Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas. Gut. 2008;57:1561–5.

    Article  PubMed  CAS  Google Scholar 

  9. Canto MI, Goggins M, Yeo CJ, Griffin C, Axilbund JE, Brune K, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2:606–21.

    Article  PubMed  Google Scholar 

  10. Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol. 2006;4:766–81 (quiz 665).

    Google Scholar 

  11. Ludwig E, Olson SH, Bayuga S, Simon J, Schattner MA, Gerdes H, et al. Feasibility and yield of screening in relatives from familial pancreatic cancer families. Am J Gastroenterol. 2011;106:946–54.

    Article  PubMed  Google Scholar 

  12. Chari ST, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology. 2008;134:95–101.

    Article  PubMed  CAS  Google Scholar 

  13. Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008;134:981–7.

    Article  PubMed  CAS  Google Scholar 

  14. Pannala R, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M, et al. Temporal association of changes in fasting blood glucose and body mass index with diagnosis of pancreatic cancer. Am J Gastroenterol. 2009;104:2318–25.

    Article  PubMed  Google Scholar 

  15. Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 1995;273:1605–9.

    Article  PubMed  CAS  Google Scholar 

  16. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA. 2005;293:194–202.

    Article  PubMed  CAS  Google Scholar 

  17. Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, et al. Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus. Diabetes Res Clin Pract. 2002;55:65–85.

    Article  PubMed  Google Scholar 

  18. Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005;129:504–11.

    PubMed  Google Scholar 

  19. Gupta S, Vittinghoff E, Bertenthal D, Corley D, Shen H, Walter LC, et al. New-onset diabetes and pancreatic cancer. Clin Gastroenterol Hepatol. 2006;4:1366–72 (quiz 1301).

    Google Scholar 

  20. Permert J, Larsson J, Westermark GT, Herrington MK, Christmanson L, Pour PM, et al. Islet amyloid polypeptide in patients with pancreatic cancer and diabetes. N Engl J Med. 1994;330:313–8.

    Article  PubMed  CAS  Google Scholar 

  21. Basso D, Greco E, Fogar P, Pucci P, Flagiello A, Baldo G, et al. Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause? Clin Chim Acta. 2006;372:120–8.

    Article  PubMed  CAS  Google Scholar 

  22. Pfeffer F, Koczan D, Adam U, Benz S, von Dobschuetz E, Prall F, et al. Expression of connexin26 in islets of Langerhans is associated with impaired glucose tolerance in patients with pancreatic adenocarcinoma. Pancreas. 2004;29:284–90.

    Article  PubMed  CAS  Google Scholar 

  23. Wang F, Larsson J, Adrian TE, Gasslander T, Permert J. In vitro influences between pancreatic adenocarcinoma cells and pancreatic islets. J Surg Res. 1998;79:13–9.

    Article  PubMed  CAS  Google Scholar 

  24. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009;137:482–8.

    Article  PubMed  Google Scholar 

  25. Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer. 2011;11:20.

    Article  PubMed  CAS  Google Scholar 

  26. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766–77.

    Article  PubMed  CAS  Google Scholar 

  27. Ferrara A, Lewis JD, Quesenberry CP Jr, Peng T, Strom BL, Van Den Eeden SK, et al. Cohort study of pioglitazone and cancer incidence in patients with diabetes. Diabetes Care. 2011;34:923–9.

    Article  PubMed  CAS  Google Scholar 

  28. Galli A, Ceni E, Crabb DW, Mello T, Salzano R, Grappone C, et al. Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPARgamma independent mechanisms. Gut. 2004;53:1688–97.

    Article  PubMed  CAS  Google Scholar 

  29. Itami A, Watanabe G, Shimada Y, Hashimoto Y, Kawamura J, Kato M, et al. Ligands for peroxisome proliferator-activated receptor gamma inhibit growth of pancreatic cancers both in vitro and in vivo. Int J Cancer. 2001;94:370–6.

    Article  PubMed  CAS  Google Scholar 

  30. Hart PA, Kamada P, Rabe KG, Srinivasan S, Basu A, Aggarwal G, et al. Weight loss precedes cancer-specific symptoms in pancreatic cancer-associated diabetes mellitus. Pancreas. 2011;40:768–72.

    Article  PubMed  Google Scholar 

  31. Gangi S, Fletcher JG, Nathan MA, Christensen JA, Harmsen WS, Crownhart BS, et al. Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis. AJR Am J Roentgenol. 2004;182:897–903.

    PubMed  Google Scholar 

  32. Pelaez-Luna M, Takahashi N, Fletcher JG, Chari ST. Resectability of presymptomatic pancreatic cancer and its relationship to onset of diabetes: a retrospective review of CT scans and fasting glucose values prior to diagnosis. Am J Gastroenterol. 2007;102:2157–63.

    Article  PubMed  Google Scholar 

  33. Satake K, Takeuchi T, Homma T, Ozaki H. CA19-9 as a screening and diagnostic tool in symptomatic patients: the Japanese experience. Pancreas. 1994;9:703–6.

    Article  PubMed  CAS  Google Scholar 

  34. Kim JE, Lee KT, Lee JK, Paik SW, Rhee JC, Choi KW. Clinical usefulness of carbohydrate antigen 19–9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol. 2004;19:182–6.

    Article  PubMed  Google Scholar 

  35. Zubarik R, Gordon SR, Lidofsky SD, Anderson SR, Pipas JM, Badger G, et al. Screening for pancreatic cancer in a high-risk population with serum CA 19–9 and targeted EUS: a feasibility study. Gastrointest Endosc. 2011;74:87–95.

    Article  PubMed  Google Scholar 

  36. Gullo L, Pezzilli R, Morselli-Labate AM. Diabetes and the risk of pancreatic cancer. N Engl J Med. 1994;331:81–4.

    Article  PubMed  CAS  Google Scholar 

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The authors declare that they have no conflict of interest

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Correspondence to Yousuke Nakai.

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Mizuno, S., Nakai, Y., Isayama, H. et al. Risk factors and early signs of pancreatic cancer in diabetes: screening strategy based on diabetes onset age. J Gastroenterol 48, 238–246 (2013). https://doi.org/10.1007/s00535-012-0622-z

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  • DOI: https://doi.org/10.1007/s00535-012-0622-z

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