Plasma adiponectin levels and endometrial cancer risk in pre- and postmenopausal women.
BACKGROUND
Adiponectin, an adipocytokine secreted by adipose tissue, is decreased in obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome, all of which are well-established risk factors for endometrial cancer.


METHODS
We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition to examine the relation between prediagnostic plasma adiponectin levels and endometrial cancer risk. Among pre- and postmenopausal women who were not currently using exogenous hormones, 284 women developed incident endometrial cancer during an average of 5.1 yr of follow-up. Using risk set sampling, 548 control subjects were selected, matched on center, age, menopausal status, phase of menstrual cycle, time of blood draw, and fasting status. Conditional logistic regression models were used to estimate relative risks and 95% confidence intervals.


RESULTS
Adiponectin levels were inversely associated with endometrial cancer risk [body mass index-adjusted relative risk for the top vs. bottom quartile = 0.56 (95% confidence interval 0.36-0.86), P(trend) = 0.006]. There was evidence of a stronger inverse association among obese women than among nonobese women (P(heterogeneity) = 0.03). The inverse association also appeared stronger for women who were postmenopausal or perimenopausal than premenopausal at baseline, but this was not statistically significantly heterogeneous (P(heterogeneity) = 0.51). The association remained statistically significant after separate adjustment for other obesity-related physiological risk factors such as C-peptide, IGF binding protein-1, IGF binding protein-2, SHBG, estrone, or free testosterone but only marginally statistically significant after simultaneous adjustment for these factors.


CONCLUSIONS
High circulating adiponectin levels are associated with reduced endometrial cancer risk, largely independent of other obesity-related risk factors.
Cust
Anne E
AE
Nutrition and Hormones Unit, International Agency for Research on Cancer, 69372 Lyon, France.
Kaaks
Rudolf
R
Friedenreich
Christine
C
Bonnet
Fabrice
F
Laville
Martine
M
Lukanova
Annekatrin
A
Rinaldi
Sabina
S
Dossus
Laure
L
Slimani
Nadia
N
Lundin
Eva
E
Tjønneland
Anne
A
Olsen
Anja
A
Overvad
Kim
K
Clavel-Chapelon
Françoise
F
Mesrine
Sylvie
S
Joulin
Virginie
V
Linseisen
Jakob
J
Rohrmann
Sabine
S
Pischon
Tobias
T
Boeing
Heiner
H
Trichopoulos
Dimitrios
D
Trichopoulou
Antonia
A
Benetou
Vassiliki
V
Palli
Domenico
D
Berrino
Franco
F
Tumino
Rosario
R
Sacerdote
Carlotta
C
Mattiello
Amalia
A
Quirós
J Ramón
JR
Mendez
Michelle A
MA
Sánchez
María-José
MJ
Larrañaga
Nerea
N
Tormo
M J
MJ
Ardanaz
Eva
E
Bueno-de-Mesquita
H Bas
HB
Peeters
Petra H M
PH
van Gils
Carla H
CH
Khaw
Kay-Tee
KT
Bingham
Sheila
S
Allen
Naomi
N
Key
Tim
T
Jenab
Mazda
M
Riboli
Elio
E
D052242:Adiponectin / Q000097:blood*; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D017697:Premenopause / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors
D052242:Adiponectin