title: Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition.
abstract: 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.
authors.affiliation: Nutrition and Hormones Unit, International Agency for Research on Cancer, Lyon, France.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cust
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Christine
authors.initials: C
authors.lastname: Friedenreich
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Mandy
authors.initials: M
authors.lastname: Schulz
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Benetou
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Tim
authors.initials: T
authors.lastname: Key
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: 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
chemical_list: D002096:C-Peptide; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2