Skip to main content

Advertisement

SpringerLink
Log in

Diabetes mellitus as a risk factor for gastrointestinal cancers among postmenopausal women

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objectives

While diabetes has been linked to several cancers in the gastrointestinal (GI) tract, findings have been mixed for sites other than colorectal and liver cancer. We used the Women’s Health Initiative (WHI) data and conducted a comprehensive assessment of associations between diabetes and GI malignancy (esophagus, stomach, liver, biliary, pancreas, colon, and rectal).

Methods

A total of 145,765 postmenopausal women aged 50–79 enrolled in the WHI were followed for a mean 10.3 years. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between GI cancers and diagnosed diabetes, including its duration and treatment.

Results

Diabetes at enrollment was associated with increased risk of liver (HR = 2.97; 95 % CI, 1.66–5.32), pancreatic (HR = 1.62; 95 % CI, 1.15–2.30), colon (HR = 1.38; 95 % CI, 1.14–1.66), and rectal (HR = 1.87, 95 % CI: 1.22–2.85) cancer. Diabetes severity, assessed by duration or need for pharmacotherapy, appeared to have stronger links to risk of liver, pancreatic, and rectal cancer, but not colon cancer. There was no statistically significant association of diabetes with biliary, esophageal, and stomach cancers.

Conclusion

Type 2 diabetes is associated with a significantly increased risk of cancers of the liver, pancreas, colon, and rectum in postmenopausal women. The suggestion that diabetes severity further increases these cancer risks requires future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Stovring H, Andersen M, Beck-Nielsen H, Green A, Vach W (2003) Rising prevalence of diabetes: evidence from a Danish pharmaco-epidemiological database. Lancet 362:537–538

    Article  PubMed  Google Scholar 

  2. Giovannucci E, Harlan DM, Archer MC et al (2010) Diabetes and cancer: a consensus report. Diabetes Care 33:1674–1685

    Article  PubMed  Google Scholar 

  3. Seshasai SR, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364:829–841

  4. Pollak M (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 8:915–928

    Article  PubMed  CAS  Google Scholar 

  5. Larsson SC, Orsini N, Wolk A (2005) Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 97:1679–1687

    Article  PubMed  Google Scholar 

  6. Berster JM, Goke B (2008) Type 2 diabetes mellitus as risk factor for colorectal cancer. Arch Physiol Biochem 114:84–98

    Article  PubMed  CAS  Google Scholar 

  7. 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 92:2076–2083

    Article  PubMed  CAS  Google Scholar 

  8. El-Serag HB, Hampel H, Javadi F (2006) The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 4:369–380

    Article  PubMed  Google Scholar 

  9. Hassan MM, Curley SA, Li D, et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer 116:1938–1946

  10. Grote VA, Becker S, Kaaks R (2011) Diabetes mellitus type 2—an independent risk factor for cancer? Exp Clin Endocrinol Diabetes 118:4–8

    Article  Google Scholar 

  11. Adami HO, Chow WH, Nyren O et al (1996) Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst 88:1472–1477

    Article  PubMed  CAS  Google Scholar 

  12. Jamal MM, Yoon EJ, Vega KJ, Hashemzadeh M, Chang KJ (2009) Diabetes mellitus as a risk factor for gastrointestinal cancer among American veterans. World J Gastroentrol 15:5274–5278

    Article  Google Scholar 

  13. Atchison EA, Gridley G, Carreon JD, Leitzmann MF, McGlynn KA (2010) Risk of cancer in a large cohort of U.S. veterans with diabetes. Int J Cancer 128:635–643

    Article  Google Scholar 

  14. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S (2006) Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 166:1871–1877

    Article  PubMed  Google Scholar 

  15. La Vecchia C, Negri E, Decarli A, Franceschi S (1997) Diabetes mellitus and the risk of primary liver cancer. Int J Cancer 73:204–207

    Article  PubMed  Google Scholar 

  16. La Vecchia C, Negri E, Decarli A, Franceschi S (1998) Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials 19:61–109

    Article  Google Scholar 

  17. Hays J, Hunt JR, Hubbell FA et al (2003) The Women’s Health Initiative recruitment methods and results. Ann Epidemiol 13:S18–S77

    Article  PubMed  Google Scholar 

  18. Jackson RD, LaCroix AZ, Cauley JA, McGowan J (2003) The Women’s Health Initiative calcium-vitamin D trial: overview and baseline characteristics of participants. Ann Epidemiol 13:S98–S106

    Article  PubMed  Google Scholar 

  19. Langer RD, White E, Lewis CE, Kotchen JM, Hendrix SL, Trevisan M (2003) The Women’s Health Initiative Observational Study: baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol 13:S107–S121

    Article  PubMed  Google Scholar 

  20. Ritenbaugh C, Patterson RE, Chlebowski RT et al (2003) The Women’s Health Initiative Dietary Modification trial: overview and baseline characteristics of participants. Ann Epidemiol 13:S87–S97

    Article  PubMed  Google Scholar 

  21. Stefanick ML, Cochrane BB, Hsia J, Barad DH, Liu JH, Johnson SR (2003) The Women’s Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants. Ann Epidemiol 13:S78–S86

    Article  PubMed  Google Scholar 

  22. Margolis KL, Lihong Q, Brzyski R et al (2008) Validity of diabetes self-reports in the Women’s Health Initiative: comparison with medication inventories and fasting glucose measurements. Clin Trials 5:240–247

    Article  PubMed  Google Scholar 

  23. Jackson JM, DeFor TA, Crain AL, et al. Validity of diabetes self-reports in the Women’s Health Initiative. J Clin Epi (in press)

  24. Hess KR (1995) Graphical methods for assessing violations of the proportional hazards assumption in cox regression. Stat Med 14:1707–1723

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  26. Walker A (1991) Observation and inference. An introduction to the methods of epidemiology. Epidemiology Resources Inc., USA

    Google Scholar 

  27. Petrides AS, Vogt C, Schulze-Berge D, Matthews D, Strohmeyer G (1994) Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis. Hepatology 19:616–627

    Article  PubMed  CAS  Google Scholar 

  28. Angulo P, Keach JC, Batts KP, Lindor KD (1999) Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30:1356–1362

    Article  PubMed  CAS  Google Scholar 

  29. Wanless IR, Lentz JS (1990) Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 12:1106–1110

    Article  PubMed  CAS  Google Scholar 

  30. Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakanuma Y (2001) Hepatocellular carcinoma arising in non-alcoholic steatohepatitis. Pathol Int 51:127–131

    Article  PubMed  CAS  Google Scholar 

  31. Davila JA (2010) Diabetes and hepatocellular carcinoma: what role does diabetes have in the presence of other known risk factors? Am J Gastroenterol 105:632–634

    Article  PubMed  Google Scholar 

  32. Sanyal A, Poklepovic A, Moyneur E, Barghout V Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin 26:2183–2191

  33. Gapstur SM, Gann PH, Lowe W, Liu K, Colangelo L, Dyer A (2000) Abnormal glucose metabolism and pancreatic cancer mortality. Jama-J Am Med Assoc 283:2552–2558

    Article  CAS  Google Scholar 

  34. Wideroff L, Gridley G, Mellemkjaer L et al (1997) Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 89:1360–1365

    Article  PubMed  CAS  Google Scholar 

  35. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159:1160–1167

    Article  PubMed  Google Scholar 

  36. Currie CJ, Poole CD, Gale EA (2009) The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 52:1766–1777

    Article  PubMed  CAS  Google Scholar 

  37. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM (2009) New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 32:1620–1625

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. A short list of WHI investigators is given in an Appendix. DW was supported by a NIDDK Career Development Award (DK081736-01) and the Houston VA HSR&D Center of Excellence (HFP90-20).

Conflict of interest

No conflict of interest exists.

Author information

Authors and Affiliations

  1. Mary Babb Randolph Cancer Center, Department of Community Medicine, School of Medicine, West Virginia University, P.O. Box 9190, Morgantown, WV, 26506, USA

    Juhua Luo

  2. Los Angeles Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA

    Rowan Chlebowski

  3. School of Public Health, University of California, Los Angeles, CA, USA

    Simin Liu

  4. Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, MD, USA

    Katherine A. McGlynn

  5. Department of Nutrition, Food Studies and Public Health, New York University, New York, NY, USA

    Niyati Parekh

  6. Sections of Health Services Research & Gastroenterology and Hepatology, Baylor College of Medicine & Clinical Epidemiology and Outcomes Program, Houston VAHSR&D Center of Excellence, Houston, TX, USA

    Donna L. White

  7. HealthPartners Research Foundation, Minneapolis, MN, USA

    Karen L. Margolis

Authors
  1. Juhua Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rowan Chlebowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katherine A. McGlynn
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Niyati Parekh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Donna L. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karen L. Margolis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juhua Luo.

Appendix: Short list of WHI investigators

Appendix: Short list of WHI investigators

Program Office: (National Heart, Lung, and Blood Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller.

Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA)

Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles Kooperberg; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings.

Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Haleh Sangi-Haghpeykar; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (Brown University, Providence, RI) Charles B. Eaton; (Emory University, Atlanta, GA) Lawrence S. Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Lisa Martin; (Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Erin LeBlanc; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V. Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E. Lewis; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F. Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Lauren Nathan; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D. Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) J. David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee Health Science Center, Memphis, TN) Karen C. Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E. Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Mara Vitolins; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Michael S. Simon.

Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luo, J., Chlebowski, R., Liu, S. et al. Diabetes mellitus as a risk factor for gastrointestinal cancers among postmenopausal women. Cancer Causes Control 24, 577–585 (2013). https://doi.org/10.1007/s10552-012-9996-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-012-9996-8

Keywords

Search

Navigation