TY - JOUR
T1 - Obesity, inflammatory markers, and endometrial cancer risk
T2 - A prospective case - control study
AU - Dossus, Laure
AU - Rinaldi, Sabina
AU - Becker, Susen
AU - Lukanova, Annekatrin
AU - Tjonneland, Anne
AU - Olsen, Anja
AU - Stegger, Jakob
AU - Overvad, Kim
AU - Chabbert-Buffet, Nathalie
AU - Jimenez-Corona, Aida
AU - Clavel-Chapelon, Francoise
AU - Rohrmann, Sabine
AU - Teucher, Birgit
AU - Boeing, Heiner
AU - Schütze, Madlen
AU - Trichopoulou, Antonia
AU - Benetou, Vassiliki
AU - Lagiou, Pagona
AU - Palli, Domenico
AU - Berrino, Franco
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Redondo, Maria Luisa
AU - Travier, Noémie
AU - Sanchez, Maria Jose
AU - Altzibar, Jone M.
AU - Chirlaque, Maria Dolores
AU - Ardanaz, Eva
AU - Bueno-de-Mesquita, H. Bas
AU - Van Duijnhoven, Fränzel J B
AU - Onland-Moret, N. Charlotte
AU - Peeters, Petra H M
AU - Hallmans, Goran
AU - Lundin, Eva
AU - Khaw, Kay Tee
AU - Wareham, Nicholas
AU - Allen, Naomi
AU - Key, Tim J.
AU - Slimani, Nadia
AU - Hainaut, Pierre
AU - Romaguera, Dora
AU - Norat, Teresa
AU - Riboli, Elio
AU - Kaaks, Rudolf
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
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U2 - 10.1677/ERC-10-0053
DO - 10.1677/ERC-10-0053
M3 - Article
C2 - 20843938
AN - SCOPUS:78649902497
VL - 17
SP - 1007
EP - 1019
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
SN - 1351-0088
IS - 4
ER -