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Diabetes and risk of pancreatic cancer: a pooled analysis of three large case–control studies

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Abstract

Racial differences in diabetes-associated pancreatic cancer (PC) and the interaction of diabetes with other risk factors are not well established. We determined the association between diabetes and risk of PC in 2,192 cases and 5,113 controls in three large case–control studies conducted at the National Cancer Institute, the University of California San Francisco, and the M.D. Anderson Cancer Center. In multivariable analyses, diabetes was associated with a 1.8-fold risk of PC [95% confidence interval (CI) = 1.5–2.1]. Risk estimates decreased with increasing years with diabetes (≤2 years OR = 2.9, 95% CI = 2.1–3.9; 3–5 years OR = 1.9, 95% CI = 1.3–2.6; 6–10 years OR = 1.6, 95% CI = 1.2–2.3; 11–15 years OR = 1.3, 95% CI = 0.9–2.0; > 15 years OR = 1.4, 95% CI = 1.0–2.0 (p for trend < 0.0001). Among diabetics, risk was higher in insulin ever users compared with nonusers (OR = 2.2, 95% CI = 1.6–3.7) and was restricted to insulin use of ≤3 years (OR = 2.4). Insulin use of >10 years was associated with a reduced risk of pancreatic cancer (OR = 0.5, 95% CI = 0.3–0.9; p for trend < 0.0001). Hispanic men and Asians had a higher risk of diabetes-associated PC than did whites and blacks, but the differences were not statistically significant. No significant interaction between diabetes and cigarette smoking, alcohol consumption and body mass index was observed. Although reverse causation may explain the association between diabetes diagnosed in close temporal proximity to PC, our results show that long-term diabetes, even though risk diminishes over time, remains a risk factor for PC independent of obesity and smoking.

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Abbreviations

AOR:

Adjusted odds ratio

BMI:

Body mass index

CI:

Confidence interval

HCFA:

Health Care Finance Administration

MDACC:

The University of Texas M.D. Anderson Cancer Center

NCI:

National Cancer Institute

OR:

Odds ratio

PC:

Pancreatic cancer

SFBA:

The University of California San Francisco Bay Area

References

  1. Gullo L, Pezzilli R (2004) Diabetes and pancreatic cancer. Pancreas 28(4):451, author reply 451–2

  2. Fisher WE (2001) Diabetes: risk factor for the development of pancreatic cancer or manifestation of the disease? World J Surg 25(4):503–508

    Article  CAS  PubMed  Google Scholar 

  3. Everhart J, Wright D (1995) Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA 273(20):1605–1609

    Article  CAS  PubMed  Google Scholar 

  4. Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M (2005) Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 92(11):2076–2083

    Article  CAS  PubMed  Google Scholar 

  5. Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A (2000) Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 283:2552–2558

    Article  CAS  PubMed  Google Scholar 

  6. Batty GD, Shipley MJ, Marmot M, Smith GD (2004) Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study. Cancer Causes Control 15:873–881

    Article  PubMed  Google Scholar 

  7. Stattin P, Bjor O, Ferrari P, Lukanova A, Lenner P, Lindahl B et al (2007) Prospective study of hyperglycemia and cancer risk. Diabetes Care 30:561–567

    Article  PubMed  Google Scholar 

  8. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM et al (2005) Fasting serum glucose level and cancer risk in Korean men and women. [see comment]. JAMA 293(2):194–202

    Article  CAS  PubMed  Google Scholar 

  9. Stolzenberg-Solomon RZ, Graubard BI, Chari S, Limburg P, Taylor PR, Virtamo J et al (2005) Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA 294(22):2872–2878

    Article  CAS  PubMed  Google Scholar 

  10. Pisani P (2008) Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch Physiol Biochem 114(1):63–70

    Article  CAS  PubMed  Google Scholar 

  11. Michaud DS, Wolpin B, Giovannucci E, Liu S, Cochrane B, Manson JE et al (2007) Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 16(10):2101–2109

    Article  CAS  PubMed  Google Scholar 

  12. Horner MJ, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N et al (2009) SEER Cancer Statistics Review 1975–2006. National Cancer Institute, Bethesda, MD

    Google Scholar 

  13. Silverman DT, Hoover RN, Brown LM, Swanson GM, Schiffman M, Greenberg RS et al (2003) Why do Black Americans have a higher risk of pancreatic cancer than White Americans? Epidemiology 14(1):45–54

    Article  PubMed  Google Scholar 

  14. Arnold LD, Patel AV, Yan Y, Jacobs EJ, Thun MJ, Calle EE et al (2009) Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity? Cancer Epidemiol Biomarkers Prev 18(9):2397–2405

    Article  PubMed  Google Scholar 

  15. Hassan MM, Wolff RA, Bondy ML, Abbruzzese JL, Vauthey J-N, Pisters PW et al (2007) Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol 102:2696–2707

    Article  PubMed  Google Scholar 

  16. Hassan MM, Abbruzzese JL, Bondy ML, Wolff RA, Vauthey JN, Pisters PW et al (2007) Passive smoking and the use of noncigarette tobacco products in association with risk for pancreatic cancer: a case-control study. Cancer 109(12):2547–2556

    Article  PubMed  Google Scholar 

  17. Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML et al (2009) Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301(24):2553–2962

    Article  CAS  PubMed  Google Scholar 

  18. Li D, Yeung SJ, Hassan MM, Konopleva M, Abbruzzese JL (2009) Antidiabetic therapy and risk of pancreatic cancer. Gastroenterology 137:482–488

    Article  PubMed  Google Scholar 

  19. Duell EJ, Holly EA, Bracci PM, Wiencke JK, Kelsey KT (2002) A population-based study of the Arg399Gln polymorphism in X-ray repair cross- complementing group 1 (XRCC1) and risk of pancreatic adenocarcinoma. Cancer Res 62(16):4630–4636

    CAS  PubMed  Google Scholar 

  20. Duell EJ, Holly EA, Bracci PM, Liu M, Wiencke JK, Kelsey KT (2002) A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. J Natl Cancer Inst 4:297–306

    Google Scholar 

  21. Slebos RJ, Hoppin JA, Tolbert PE, Holly EA, Brock JW, Zhang RH et al (2000) K-ras and p53 in pancreatic cancer: association with medical history, histopathology, and environmental exposures in a population-based study. Cancer Epidemiol Biomarkers Prev 9(11):1223–1232

    CAS  PubMed  Google Scholar 

  22. Hoppin JA, Tolbert PE, Holly EA, Brock JW, Korrick SA, Altshul LM et al (2000) Pancreatic cancer and serum organochlorine levels. Cancer Epidemiol Biomarkers Prev 9(2):199–205

    CAS  PubMed  Google Scholar 

  23. Wang F, Gupta S, Holly EA (2006) Diabetes mellitus and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area, California. Cancer Epidemiol Biomarkers Prev 15(8):1458–1463

    Article  PubMed  Google Scholar 

  24. Eberle CA, Bracci PM, Holly EA (2005) Anthropometric factors and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area. Cancer Causes Control 16(10):1235–1244

    Article  PubMed  Google Scholar 

  25. Chan JM, Wang F, Holly EA (2005) Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco Bay Area. Cancer Epidemiol Biomarkers Prev 14(9):2093–2097

    Article  PubMed  Google Scholar 

  26. Duell EJ, Holly EA (2005) Reproductive and menstrual risk factors for pancreatic cancer: a population-based study of San Francisco Bay Area women. Am J Epidemiol 161(8):741–747

    Article  PubMed  Google Scholar 

  27. Holly EA, Eberle CA, Bracci PM (2003) Prior history of allergies and pancreatic cancer in the San Francisco Bay Area. Am J Epidemiol 158(5):432–441

    Article  PubMed  Google Scholar 

  28. Ji BT, Silverman DT, Stewart PA, Blair A, Swanson GM, Baris D et al (2001) Occupational exposure to pesticides and pancreatic cancer. Am J Ind Med 39(1):92–99

    Article  CAS  PubMed  Google Scholar 

  29. Silverman DT, Schiffman M, Everhart J, Goldstein A, Lillemoe KD, Swanson GM et al (1999) Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer 80(11):1830–1837

    Article  CAS  PubMed  Google Scholar 

  30. Silverman DT, Dunn JA, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB et al (1994) Cigarette smoking and pancreas cancer: a case-control study based on direct interviews. J Natl Cancer Inst 86(20):1510–1516

    Article  CAS  PubMed  Google Scholar 

  31. Silverman DT, Swanson CA, Gridley G, Wacholder S, Greenberg RS, Brown LM et al (1998) Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst 90(22):1710–1719

    Article  CAS  PubMed  Google Scholar 

  32. Silverman DT (2001) Risk factors for pancreatic cancer: a case-control study based on direct interviews. Teratog Carcinog Mutagen 21(1):7–25

    Article  CAS  PubMed  Google Scholar 

  33. Alguacil J, Silverman DT (2004) Smokeless and other noncigarette tobacco use and pancreatic cancer: a case-control study based on direct interviews. Cancer Epidemiol Biomarkers Prev 13:55–58

    Article  CAS  PubMed  Google Scholar 

  34. Silverman DT, Brown LM, Hoover RN, Schiffman M, Lillemoe KD, Schoenberg JB et al (1995) Alcohol and pancreatic cancer in blacks and whites in the United States. Cancer Res 55:4899–4905

    CAS  PubMed  Google Scholar 

  35. Silverman DT (1996) Diagnostic certainty in pancreatic cancer. L Clin Epidemiol 49(5):3

    Google Scholar 

  36. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  37. Chari ST, Leibson CL, Rabe KG, Timmons LJ, Ransom J, de Andrade M et al (2008) Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 134(1):95–101

    Article  CAS  PubMed  Google Scholar 

  38. Pannala R et al (2008) Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology 134(4):981–987

    Article  CAS  PubMed  Google Scholar 

  39. Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330:1304–1305

    Article  PubMed  Google Scholar 

  40. Bowker SL, Majumdar SR, Veugelers P, Johnson JA (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29(2):254–258

    Article  PubMed  Google Scholar 

  41. Bonelli L, Aste H, Bovo P, Cavallini G, Felder M, Gusmaroli R et al (2003) Exocrine pancreatic cancer, cigarette smoking, and diabetes mellitus: a case-control study in northern Italy. Pancreas 27(2):143–149

    Article  PubMed  Google Scholar 

  42. Cavanaugh KL, Merkin SS, Plantinga LC, Fink NE, Sadler JH, Powe NR (2008) Accuracy of patients’ reports of comorbid disease and their association with mortality in ESRD. Am J Kidney Dis 52(1):118–127

    Article  PubMed  Google Scholar 

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Acknowledgments

Grant support is given by National Institute of Health, NCI grants CA59706, CA89726, CA108370, CA109767 (Holly E.A.: PI), CA98380 (Li D.: PI), The Rombauer Pancreatic Cancer Research Fund (UCSF) and The Lockton Pancreatic Cancer Research Fund (MDACC). The NCI study was supported by the intramural program of the Division of Cancer Epidemiology and Genetics of the National Cancer institute (Silverman D.T.: PI).

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, TX, 77030, USA

    Donghui Li, Hongwei Tang & Manal M. Hassan

  2. Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA, USA

    Elizabeth A. Holly & Paige M. Bracci

  3. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Debra T. Silverman

Authors
  1. Donghui Li
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  2. Hongwei Tang
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  3. Manal M. Hassan
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  4. Elizabeth A. Holly
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  5. Paige M. Bracci
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  6. Debra T. Silverman
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Corresponding author

Correspondence to Donghui Li.

Additional information

Paige M. Bracci and Debra T. Silverman share the senior authorship.

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Li, D., Tang, H., Hassan, M.M. et al. Diabetes and risk of pancreatic cancer: a pooled analysis of three large case–control studies. Cancer Causes Control 22, 189–197 (2011). https://doi.org/10.1007/s10552-010-9686-3

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  • DOI: https://doi.org/10.1007/s10552-010-9686-3

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