A Prospective Evaluation of Insulin and Insulin-like Growth Factor-I as Risk Factors for Endometrial Cancer

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 4; pp. 921 - 929
• Main Authors: Gunter, Marc J., Hoover, Donald R., Yu, Herbert, Wassertheil-Smoller, Sylvia, Manson, JoAnn E., Li, Jixin, Harris, Tiffany G., Rohan, Thomas E., Xue, XiaoNan, 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 D.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.04.2008
• Subjects: Aged; Body Mass Index; Carcinoma, Endometrioid - blood; Carcinoma, Endometrioid - etiology; Carcinoma, Endometrioid - metabolism; endometrial cancer; Endometrial Neoplasms - blood; Endometrial Neoplasms - etiology; Endometrial Neoplasms - metabolism; Estradiol - blood; Female; Humans; Hypoglycemic Agents - blood; IGF-I; Insulin; Insulin - blood; Insulin-Like Growth Factor Binding Protein 1 - blood; Insulin-Like Growth Factor Binding Protein 3 - blood; Middle Aged; Multicenter Studies as Topic; Obesity - complications; Proportional Hazards Models; Prospective Studies; Risk Factors
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-2686

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 (HR q4-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 (HR q4-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 (HR q4-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)