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, Xiaonan (Nan) Xue, Gloria Y F Ho, Mark H. Einstein, Robert C. Kaplan, Robert D. Burk, Judith Wylie-Rosett, Michael N. Pollak, Garnet Anderson, Barbara V. Howard, Howard Strickler

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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.

Original languageEnglish (US)
Pages (from-to)921-929
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number4
DOIs
StatePublished - Apr 2008

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Endometrioid Carcinoma
Endometrial Neoplasms
Insulin-Like Growth Factor I
Insulin
Estradiol
Hormones
Confidence Intervals
Estrogens
Obesity
Insulin-Like Growth Factor Binding Protein 3
Hyperinsulinism
Women's Health
Mitogens
Proportional Hazards Models
Observational Studies
Fasting
Cohort Studies
Prospective Studies
Glucose
Therapeutics

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. / Gunter, Marc J.; Hoover, Donald R.; Yu, Herbert; Wassertheil-Smoller, Sylvia; Manson, Joann E.; Li, Jixin; Harris, Tiffany G.; Rohan, Thomas E.; Xue, Xiaonan (Nan); Ho, Gloria Y F; Einstein, Mark H.; Kaplan, Robert C.; Burk, Robert D.; Wylie-Rosett, Judith; Pollak, Michael N.; Anderson, Garnet; Howard, Barbara V.; Strickler, Howard.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 17, No. 4, 04.2008, p. 921-929.

Research output: Contribution to journalArticle

Gunter, MJ, Hoover, DR, Yu, H, Wassertheil-Smoller, S, Manson, JE, Li, J, Harris, TG, Rohan, TE, Xue, XN, Ho, GYF, Einstein, MH, Kaplan, RC, Burk, RD, Wylie-Rosett, J, Pollak, MN, Anderson, G, Howard, BV & Strickler, H 2008, 'A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer', Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 4, pp. 921-929. https://doi.org/10.1158/1055-9965.EPI-07-2686
Gunter, Marc J. ; Hoover, Donald R. ; Yu, Herbert ; Wassertheil-Smoller, Sylvia ; Manson, Joann E. ; Li, Jixin ; Harris, Tiffany G. ; Rohan, Thomas E. ; Xue, Xiaonan (Nan) ; Ho, Gloria Y F ; Einstein, Mark H. ; Kaplan, Robert C. ; Burk, Robert D. ; Wylie-Rosett, Judith ; Pollak, Michael N. ; Anderson, Garnet ; Howard, Barbara V. ; Strickler, Howard. / A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2008 ; Vol. 17, No. 4. pp. 921-929.
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