Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European Prospective Investigation into Cancer and Nutrition

Anne E. Cust, Naomi E. Allen, Sabina Rinaldi, Laure Dossus, Christine Friedenreich, Anja Olsen, Anne Tjønneland, Kim Overvad, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Jakob Linseisen, Jenny Chang-Claude, Heiner Boeing, Mandy Schulz, Vassiliki Benetou, Antonia Trichopoulou, Dimitrios Trichopoulos, Domenico Palli, Franco Berrino, Rosario TuminoAmalia Mattiello, Paolo Vineis, J. Ramón Quirós, Antonio Agudo, Maria Jose Sánchez, Nerea Larrañaga, Carmen Navarro, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Petra H M Peeters, Carla H. Van Gils, Sheila Bingham, Kay Tee Khaw, Tim Key, Nadia Slimani, Elio Riboli, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

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], ptrend = 0.001, and decreasing serum levels of IGFBP-2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], ptrend = 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], ptrend = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], ptrend = 0.74 for IGFBP-2; and 1.08 [95% CI 0.65-1.78], ptrend = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (≤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], ptrend = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.

Original languageEnglish
Pages (from-to)2656-2664
Number of pages9
JournalInternational Journal of Cancer
Volume120
Issue number12
DOIs
Publication statusPublished - Jun 15 2007

Keywords

  • C-peptide
  • Endometrial cancer
  • IGFBP-1
  • IGFBP-2
  • Insulin
  • Prospective

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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