Case–control study of markers of insulin resistance and endometrial cancer risk

Markers of insulin resistance such as the adiponectin:leptin ratio (A:L) and the homeostasis model assessment ratio (HOMA-IR) are associated with obesity and hyperinsulinemia, both established risk factors for endometrial cancer, and may therefore be informative regarding endometrial cancer risk. This study investigated the association between endometrial cancer risk and markers of insulin resistance, namely adiponectin, leptin, the A:L ratio, insulin, fasting glucose, and the HOMA-IR. We analyzed data from 541 incident endometrial cancer cases and 961 frequency age-matched controls in a population-based case-control study in Alberta, Canada from 2002 to 2006. Participants completed interview-administered questionnaires were assessed for anthropometric measures, and provided 8-h fasting blood samples either pre- or postoperatively. Blood was analyzed for concentrations of leptin, adiponectin, and insulin by immunoassay, and fasting plasma glucose levels were determined by fluorimetric quantitative determination. Compared with the lowest quartile, the highest quartile of insulin and HOMA-IR was associated with 64% (95% confidence intervals (CI): 1.12-2.40) and 72% (95% CI: 1.17-2.53) increased risks of endometrial cancer, respectively, and the highest quartile of adiponectin was associated with a 45% (95% CI: 0.37-0.80) decreased risk after multivariable adjustments. Null associations were observed between fasting glucose, leptin and A:L, and endometrial cancer risk. This population-based study provides evidence for a role of insulin resistance in endometrial cancer etiology and may provide one possible pathway whereby obesity increases the risk of this common cancer. Interventions aimed at decreasing both obesity and insulin resistance may decrease endometrial cancer risk.