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Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.

Original publication

DOI

10.1677/ERC-10-0053

Type

Journal article

Journal

Endocrine-related cancer

Publication Date

12/2010

Volume

17

Pages

1007 - 1019

Addresses

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany.

Keywords

Humans, Endometrial Neoplasms, Obesity, Inflammation, C-Reactive Protein, Interleukin-6, Body Mass Index, Immunoassay, Logistic Models, Odds Ratio, Risk, Risk Factors, Case-Control Studies, Prospective Studies, Age Factors, Aged, Middle Aged, Female, Interleukin 1 Receptor Antagonist Protein, Biomarkers