A Prospective Evaluation of Insulin and Insulin-like Growth Factor-I as Risk Factors for Endometrial Cancer
- Marc J. Gunter1,
- Donald R. Hoover3,
- Herbert Yu4,
- Sylvia Wassertheil-Smoller1,
- JoAnn E. Manson5,
- Jixin Li3,
- Tiffany G. Harris1,
- Thomas E. Rohan1,
- XiaoNan Xue1,
- Gloria Y.F. Ho1,
- Mark H. Einstein2,
- Robert C. Kaplan1,
- Robert D. Burk1,
- Judith Wylie-Rosett1,
- Michael N. Pollak6,
- Garnet Anderson7,
- Barbara V. Howard8 and
- Howard D. Strickler1
- 1Albert Einstein College of Medicine and 2Montefiore Medical Center, New York, New York; 3Rutgers University, New Brunswick, New Jersey; 4Yale University School of Medicine, New Haven, Connecticut; 5Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; 6McGill University, Montreal, Quebec, Canada; 7Fred Hutchinson Cancer Research Center, Seattle, Washington; and 8MedStar Research Institute, Hyattsville, Maryland
- Requests for reprints:
Marc Gunter, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461. Phone: 718-430-3089; Fax: 718-430-8780. E-mail: mgunter{at}aecom.yu.edu
Abstract
Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HRq4-q1), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HRq4-q1, 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HRq4-q1, 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data. (Cancer Epidemiol Biomarkers Prev 2008;17(4):921–9)
Footnotes
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Grant support: National Cancer Institute grant R01-CA93881-01 (H. Strickler) and the Albert Einstein Cancer Center, New York (M.J. Gunter and H.D. Strickler). The Women's Health Initiative program is funded by the National Heart, Lung and Blood Institute, U.S. Department of Health and Human Services.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 22, 2008.
- Received October 10, 2007.
- Revision received January 18, 2008.
