title: Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study.
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.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Susen
authors.initials: S
authors.lastname: Becker
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Jakob
authors.initials: J
authors.lastname: Stegger
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chabbert-Buffet
authors.forename: Aida
authors.initials: A
authors.lastname: Jimenez-Corona
authors.forename: Francoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Sabine
authors.initials: S
authors.lastname: Rohrmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Teucher
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Madlen
authors.initials: M
authors.lastname: Schütze
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Benetou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Redondo
authors.forename: Noémie
authors.initials: N
authors.lastname: Travier
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Sanchez
authors.forename: Jone M
authors.initials: JM
authors.lastname: Altzibar
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Fränzel J B
authors.initials: FJ
authors.lastname: van Duijnhoven
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Goran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wareham
authors.forename: Naomi
authors.initials: N
authors.lastname: Allen
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Key
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Dora
authors.initials: D
authors.lastname: Romaguera
authors.forename: Teresa
authors.initials: T
authors.lastname: Norat
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000097:blood / Q000150:complications*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016015:Logistic Models; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications*; D016017:Odds Ratio; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D002097:C-Reactive Protein