Skip to main content

Advertisement

Log in

Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel

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

Abstract

Purpose

Gestational diabetes mellitus (GDM), a state of glucose intolerance associated with pregnancy, is increasing in prevalence. Data regarding the cancer risk associated with GDM are sparse and limited to cancers of the breast and pancreas. This study was conducted to examine the risk of incident overall and site-specific malignancies associated with prior GDM in a historical cohort of women in a large health maintenance organization in Israel.

Methods

All pregnant women aged 15–50 years who underwent 50-g glucose challenge tests between 13 March 1995 and 27 May 2009, without history of malignancy, diabetes, and infertility, were included. Clinical and demographic parameters at index date including age, socioeconomic level, BMI, and parity were collected. Diagnosis of gestational diabetes was based on the 100-g oral glucose tolerance test using Carpenter and Coustan criteria. Cancer diagnoses were obtained from the Israel Cancer Register through linkage data.

Results

Among the 185,315 women who had undergone glucose challenge during the study period, 11,264 (6.1%) were diagnosed with GDM. During a total follow-up period of 1.05 million person-years (mean = 5.19 ± 3.9, median = 4.3), 2,034 incident cases of cancer were identified. GDM was associated with a hazard ratio (HR) of 7.06 (95% CI: 1.69–29.45) for pancreatic cancer (nine cases) and a HR of 1.70 (95% CI: 0.97–2.99) for hematological malignancies (177 cases). The association between GDM and hematological malignancies was limited to women with 5 or more years of follow-up (HR = 4.53; 95% CI: 1.81–11.31).

Conclusion

GDM is associated with an increased risk of pancreatic cancer and hematologic malignancies.

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

Access this article

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

Abbreviations

GDM:

Gestational diabetes mellitus

DM:

Diabetes mellitus

GCT:

Glucose challenge test

OGTT:

Oral glucose tolerance test

HMO:

Health maintenance organization

MHS:

Maccabi healthcare services

NHL:

Non-hodgkin’s lymphoma

AML:

Acute myeloid leukemia

References

  1. Metzger BE, Coustan DR (1998) Summary and recommendations of the fourth international workshop-conference on gestational diabetes mellitus. The organizing committee. Diabetes Care 21(Suppl 2):B161–B167

    Google Scholar 

  2. Buchanan TA, Xiang A, Kjos SL, Watanabe R (2007) What is gestational diabetes? Diabetes Care 30(Suppl 2):S105–S111

    Article  PubMed  CAS  Google Scholar 

  3. Ferrara A, Hedderson MM, Quesenberry CP, Selby JV (2002) Prevalence of gestational diabetes mellitus detected by the national diabetes data group or the carpenter and coustan plasma glucose thresholds. Diabetes Care 25(9):1625–1630

    Article  PubMed  Google Scholar 

  4. Dornhorst A, Paterson CM, Nicholls JS, Wadsworth J, Chiu DC, Elkeles RS, Johnston DG, Beard RW (1992) High prevalence of gestational diabetes in women from ethnic minority groups. Diabet Med 9(9):820–825

    Article  PubMed  CAS  Google Scholar 

  5. Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS (2005) Increasing prevalence of gestational diabetes (GDM) over time and by birth cohort: Kaiser Permanente of colorado GDM screening program. Diabetes Care 28(3):579–584

    Article  PubMed  Google Scholar 

  6. Ferrara A (2007) Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care 30(Suppl 2):S141–S146

    Article  PubMed  Google Scholar 

  7. Kjos SL, Buchanan TA (1999) Gestational diabetes mellitus. N Engl J Med 341(23):1749–1756

    Article  PubMed  CAS  Google Scholar 

  8. Metzger BE (2007) Long-term outcomes in mothers diagnosed with gestational diabetes mellitus and their offspring. Clin Obstet Gynecol 50(4):972–979

    Article  PubMed  Google Scholar 

  9. Chodick G, Elchalal U, Sella T, Heymann A, Porath A, Kokia E, Shalev V (2010) The risk of overt diabetes mellitus among women with gestational diabetes: a population-based study. Diabet Med 27(7):779–785

    Article  PubMed  CAS  Google Scholar 

  10. Saydah SH, Loria CM, Eberhardt MS, Brancati FL (2003) Abnormal glucose tolerance and the risk of cancer death in the United States. Am J Epidemiol 157(12):1092–1100

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. Zhou XH, Qiao Q, Zethelius B, Pyörälä K, Söderberg S, Pajak A, Stehouwer CD, Heine RJ, Jousilahti P, Ruotolo G, Nilsson PM, Calori G, Tuomilehto J, The DECODE Study Group (2010) Diabetes, prediabetes and cancer mortality. Diabetologia 53(9):1867–1876

    Article  PubMed  CAS  Google Scholar 

  13. 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(12):1160–1167

    Article  PubMed  Google Scholar 

  14. Chodick G, Heymann A, Rosenmann L, Green M, Flash S, Porath A, Kokia E, Shalev V (2010) Diabetes and risk of incident cancer: a large population-based cohort study in Israel. Cancer Causes Control 21(6):879–887

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  16. Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, Persson I (1991) Cancer risk in patients with diabetes mellitus. Cancer Causes Control 2(5):307–314

    Article  PubMed  CAS  Google Scholar 

  17. La Vecchia C, Negri E, Franceschi S, D’Avanzo B, Boyle P (1994) A case–control study of diabetes mellitus and cancer risk. Br J Cancer 70(5):950–953

    Article  PubMed  CAS  Google Scholar 

  18. Xue F, Michels KB (2007) Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. Am J Clin Nutr 86(3):S823–S835

    PubMed  Google Scholar 

  19. Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schünemann HJ, Ram M, Freudenheim JL, Sieri S, Trevisan M, Berrino F (2002) Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomark Prev 11(11):1361–1368

    CAS  Google Scholar 

  20. Adler AI, Weiss NS, Kamb ML, Lyon JL (1996) Is diabetes mellitus a risk factor for ovarian cancer? A case–control study in Utah and Washington (United States). Cancer Causes Control 7(4):475–478

    Article  PubMed  CAS  Google Scholar 

  21. Dawson S (2004) Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Cancer 100(1):149–155

    Article  PubMed  Google Scholar 

  22. Perrin M, Terry M, Kleinhaus K, Yanetz R, Tiram E, Calderon-Margalit R, Friedlander Y, Paltiel O, Harlap S (2008) Gestational diabetes and the risk of breast cancer among women in the Jerusalem Perinatal Study. Breast Cancer Res Treat 108(1):129–135

    Article  PubMed  CAS  Google Scholar 

  23. Perrin MC, Terry MB, Kleinhaus K, Deutsch L, Yanetz R, Tiram E, Calderon R, Friedlander Y, Paltiel O, Harlap S (2007) Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study. BMC Med 5:25. doi:1741-7015-5-25

    Article  PubMed  CAS  Google Scholar 

  24. Nechuta S, Paneth N, Velie E (2010) Pregnancy characteristics and maternal breast cancer risk: a review of the epidemiologic literature. Cancer Causes Control 21(7):967–989

    Article  PubMed  Google Scholar 

  25. Bendelac J (2009) Membership in sick funds 2008. National Insurance Institute, Jerusalem

    Google Scholar 

  26. Chodick G, Heymann A, Shalev V, Kookia E (2003) The epidemiology of diabetes in a large Israeli HMO. Eur J Epidemiol 18:1143–1146

    Article  PubMed  Google Scholar 

  27. American Diabetes Association (2003) Gestational diabetes mellitus. Diabetes Care 26(Suppl 1):S103–S105

    Google Scholar 

  28. Carpenter M, Coustan D (1982) Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 144:768–773

    PubMed  CAS  Google Scholar 

  29. Israel Center for Disease Control (2003) Investigation into the completeness for the Israel cancer registry. Israel Center for Disease Control Publication 230 (In Hebrew), Jerusalem

  30. World Health Organization (1998) Obesity: preventing and managing the global epidemic. Report of a WHO consultation on obesity, 3–5 June 1997. World Health Organization, Geneva, Switzerland

  31. Israel Central Bureau of Statistics (1998) 1995 Census of population and housing, Jerusalem

  32. Cox DR (1972) Regression models and life tables (with discussion). J R Stat Soc B 32:187–220

    Google Scholar 

  33. 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  PubMed  CAS  Google Scholar 

  34. Karna E, Surazynski A, Orlowski K, Laszkiewicz J, Puchalski Z, Nawrat P, Palka J (2002) Serum and tissue level of insulin-like growth factor-I (IGF-I) and IGF-I binding proteins as an index of pancreatitis and pancreatic cancer. Int J Exp Pathol 83(5):239–245

    Article  PubMed  CAS  Google Scholar 

  35. Bergmann U, Funatomi H, Yokoyama M, Beger HG, Korc M (1995) Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res 55(10):2007–2011

    PubMed  CAS  Google Scholar 

  36. Li D, Abbruzzese JL (2010) New strategies in pancreatic cancer: emerging epidemiologic and therapeutic concepts. Clin Cancer Res 16(17):4313–4318

    Article  PubMed  CAS  Google Scholar 

  37. Lisker S, Brody J, Beizer L (1966) Abnormal carbohydrate metabolism in patients with malignant blood dyscrasias. Am J Med Sci 252:282–288

    Article  PubMed  CAS  Google Scholar 

  38. Mitri J, Castillo J, Pittas A (2008) Diabetes and risk of non-Hodgkin’s lymphoma: a meta-analysis of observational studies. Diabetes Care 31:2391–2397

    Article  PubMed  Google Scholar 

  39. PJ ChaoC (2008) Type 2 diabetes mellitus and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis. Am J Epidemiol 168(5):471–480

    Article  Google Scholar 

  40. Cerhan J, Wallace R, Folsom A, Potter J, Sellers T, Zheng W, Lutz C (1997) Medical history risk factors for non-Hodgkin’s lymphoma in older women. J Natl Cancer Inst 89(4):314–318

    PubMed  CAS  Google Scholar 

  41. Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A (1997) Cancer and diabetes—a follow-up study of two population-based cohorts of diabetic patients. J Intern Med 241(6):471–475

    Article  PubMed  CAS  Google Scholar 

  42. Cerhan JR, Bernstein L, Severson RK, Davis S, Colt JS, Blair A, Hartge P (2005) Anthropometrics, physical activity, related medical conditions, and the risk of non-hodgkin lymphoma. Cancer Causes Control 16(10):1203–1214

    Article  PubMed  Google Scholar 

  43. Troisi R, Weiss H, Hoover R (1998) Pregnancy characteristics and maternal risk of breast cancer. Epidemiology 9(6):641–647

    Article  PubMed  CAS  Google Scholar 

  44. Rollison DE, Giuliano AR, Sellers TA, Laronga C, Sweeney C, Risendal B, Baumgartner KB, Byers T, Slattery ML (2008) Population-based case–control study of diabetes and breast cancer risk in Hispanic and non-Hispanic White women living in US southwestern states. Am J Epidemiol 167(4):447–456

    Article  PubMed  Google Scholar 

  45. Haver M, Locksmith G, Emmet E (2003) Irregular menses: an independent risk factor for gestational diabetes mellitus. Am J Obstet Gynecol 188(5):1189–1191

    Article  PubMed  Google Scholar 

  46. Clavel-Chapelon F, E3N Group (2002) Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women. Cancer Causes Control 13(9):831–838

    Article  PubMed  CAS  Google Scholar 

  47. Bassett JK, Severi G, English DR, Baglietto L, Krishnan K, Hopper JL, Giles GG (2010) Body size, weight change, and risk of colon cancer. Cancer Epidemiol Biomark Prev 19(11):2978–2986

    Article  Google Scholar 

  48. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578

    Article  PubMed  Google Scholar 

  49. U.S. Cancer Statistics Working Group (2010) United States cancer statistics: 1999–2006 incidence and mortality web-based report. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, Atlanta, US

  50. American Cancer Society (2010) Cancer facts and figures 2010. American Cancer Society, Atlanta, GA

    Google Scholar 

Download references

Conflict of interests

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tal Sella.

Additional information

Tal Sella and Gabriel Chodick equally contributed to the study and manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sella, T., Chodick, G., Barchana, M. et al. Gestational diabetes and risk of incident primary cancer: a large historical cohort study in Israel. Cancer Causes Control 22, 1513–1520 (2011). https://doi.org/10.1007/s10552-011-9825-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-011-9825-5

Keywords

Navigation