Obesity, inflammatory markers, and endometrial cancer risk: A prospective case - control study

Laure Dossus, Sabina Rinaldi, Susen Becker, Annekatrin Lukanova, Anne Tjonneland, Anja Olsen, Jakob Stegger, Kim Overvad, Nathalie Chabbert-Buffet, Aida Jimenez-Corona, Francoise Clavel-Chapelon, Sabine Rohrmann, Birgit Teucher, Heiner Boeing, Madlen Schütze, Antonia Trichopoulou, Vassiliki Benetou, Pagona Lagiou, Domenico Palli, Franco BerrinoSalvatore Panico, Rosario Tumino, Carlotta Sacerdote, Maria Luisa Redondo, Noémie Travier, Maria Jose Sanchez, Jone M. Altzibar, Maria Dolores Chirlaque, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Fränzel J B Van Duijnhoven, N. Charlotte Onland-Moret, Petra H M Peeters, Goran Hallmans, Eva Lundin, Kay Tee Khaw, Nicholas Wareham, Naomi Allen, Tim J. Key, Nadia Slimani, Pierre Hainaut, Dora Romaguera, Teresa Norat, Elio Riboli, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

Abstract

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, Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, Ptrend=0. 008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, Ptrend=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 languageEnglish
Pages (from-to)1007-1019
Number of pages13
JournalEndocrine-Related Cancer
Volume17
Issue number4
DOIs
Publication statusPublished - Dec 2010

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

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