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Multicenter Study
. 2010 Oct 29;17(4):1007-19.
doi: 10.1677/ERC-10-0053. Print 2010 Dec.

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

Laure Dossus  1 , 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 Berrino, Salvatore 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
Affiliations
Multicenter Study

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

Laure Dossus et al. Endocr Relat Cancer. .

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, 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.

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Figures

Figure 1
Figure 1
Risk (OR (95% CI)) of endometrial cancer for IL6 on a continuous log2 scale adjusted for BMI, and stratified by menopausal status and lag time to cancer diagnosis.
See this image and copyright information in PMC

References

    1. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link? Biochemical Pharmacology. 2006;72:1605–1621. doi: 10.1016/j.bcp.2006.06.029. - DOI - PubMed
    1. Allen NE, Key TJ, Dossus L, Rinaldi S, Cust A, Lukanova A, Peeters PH, Onland-Moret NC, Lahmann PH, Berrino F, et al. Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC) Endocrine-Related Cancer. 2008;15:485–497. doi: 10.1677/ERC-07-0064. - DOI - PMC - PubMed
    1. Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: role in biology. Annual Review of Immunology. 1998;16:27–55. doi: 10.1146/annurev.immunol.16.1.27. - DOI - PubMed
    1. Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. Journal of Clinical Endocrinology and Metabolism. 2002;87:2084–2089. doi: 10.1210/jc.87.5.2084. - DOI - PubMed
    1. Bellone S, Watts K, Cane’ S, Palmieri M, Cannon MJ, Burnett A, Roman JJ, Pecorelli S, Santin AD. High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer. Gynecologic Oncology. 2005;98:92–98. doi: 10.1016/j.ygyno.2005.03.016. - DOI - PubMed

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