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A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.

Original publication

DOI

10.1093/aje/kws309

Type

Journal article

Journal

Am J Epidemiol

Publication Date

15/04/2013

Volume

177

Pages

787 - 799

Keywords

Adiponectin, Aged, Biomarkers, Blood Glucose, Body Mass Index, C-Reactive Protein, Case-Control Studies, Cholesterol, Cohort Studies, Endometrial Neoplasms, Estrogens, European Union, Factor Analysis, Statistical, Female, Follow-Up Studies, Germany, Humans, Incidence, Inflammation, Interleukin-1, Interleukin-6, Life Style, Middle Aged, Postmenopause, Premenopause, Prospective Studies, Risk Assessment, Risk Factors, Somatomedins, Triglycerides, Tumor Necrosis Factor-alpha, Waist Circumference