Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition.
We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre- and post-menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow-up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP-2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.57], p(trend) = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP-2; and 1.08 [95% CI 0.65-1.78], p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (< or =< or =6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67-2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.
Cust
Anne E
AE
Nutrition and Hormones Unit, International Agency for Research on Cancer, Lyon, France.
Allen
Naomi E
NE
Rinaldi
Sabina
S
Dossus
Laure
L
Friedenreich
Christine
C
Olsen
Anja
A
Tjønneland
Anne
A
Overvad
Kim
K
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Linseisen
Jakob
J
Chang-Claude
Jenny
J
Boeing
Heiner
H
Schulz
Mandy
M
Benetou
Vassiliki
V
Trichopoulou
Antonia
A
Trichopoulos
Dimitrios
D
Palli
Domenico
D
Berrino
Franco
F
Tumino
Rosario
R
Mattiello
Amalia
A
Vineis
Paolo
P
Quirós
J Ramón
JR
Agudo
Antonio
A
Sánchez
Maria-Jose
MJ
Larrañaga
Nerea
N
Navarro
Carmen
C
Ardanaz
Eva
E
Bueno-de-Mesquita
H Bas
HB
Peeters
Petra H M
PH
van Gils
Carla H
CH
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Key
Tim
T
Slimani
Nadia
N
Riboli
Elio
E
Kaaks
Rudolf
R
D000368:Aged; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000097:blood* / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D016015:Logistic Models; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires
D002096:C-Peptide; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2