Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study.
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.
Dossus
Laure
L
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany.
Rinaldi
Sabina
S
Becker
Susen
S
Lukanova
Annekatrin
A
Tjonneland
Anne
A
Olsen
Anja
A
Stegger
Jakob
J
Overvad
Kim
K
Chabbert-Buffet
Nathalie
N
Jimenez-Corona
Aida
A
Clavel-Chapelon
Francoise
F
Rohrmann
Sabine
S
Teucher
Birgit
B
Boeing
Heiner
H
Schütze
Madlen
M
Trichopoulou
Antonia
A
Benetou
Vassiliki
V
Lagiou
Pagona
P
Palli
Domenico
D
Berrino
Franco
F
Panico
Salvatore
S
Tumino
Rosario
R
Sacerdote
Carlotta
C
Redondo
Maria-Luisa
ML
Travier
Noémie
N
Sanchez
Maria-Jose
MJ
Altzibar
Jone M
JM
Chirlaque
Maria-Dolores
MD
Ardanaz
Eva
E
Bueno-de-Mesquita
H Bas
HB
van Duijnhoven
Fränzel J B
FJ
Onland-Moret
N Charlotte
NC
Peeters
Petra H M
PH
Hallmans
Goran
G
Lundin
Eva
E
Khaw
Kay-Tee
KT
Wareham
Nicholas
N
Allen
Naomi
N
Key
Tim J
TJ
Slimani
Nadia
N
Hainaut
Pierre
P
Romaguera
Dora
D
Norat
Teresa
T
Riboli
Elio
E
Kaaks
Rudolf
R
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
D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D002097:C-Reactive Protein