A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer

Marc J. Gunter, Donald R. Hoover, Herbert Yu, Sylvia Wassertheil-Smoller, Joann E. Manson, Jixin Li, Tiffany G. Harris, Thomas E. Rohan, Xiao Nan Xue, Gloria Yuen Fun Ho, Mark H. Einstein, Robert C. Kaplan, Robert D. Burk, Judith Wylie-Rosett, Michael N. Pollak, Garnet Anderson, Barbara V. Howard, Howard D. Strickler

Research output: Contribution to journalArticlepeer-review

208 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)921-929
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Issue number4
StatePublished - Apr 2008

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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