Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer

Annekatrin Lukanova, Anne Zeleniuch-Jacquotte, Eva Lundin, Andrea Micheli, Alan A. Arslan, Sabina Rinaldi, Paola Muti, Per Lenner, Karen L. Koenig, Carine Biessy, Vittorio Krogh, Elio Riboli, Roy E. Shore, Par Stattin, Franco Berrino, Göran Hallmans, Paolo Toniolo, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review


Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (Ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [Ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [P trend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.

Original languageEnglish
Pages (from-to)262-268
Number of pages7
JournalInternational Journal of Cancer
Issue number2
Publication statusPublished - Jan 10 2004


  • C-peptide
  • Cohort study
  • Endometrial cancer
  • Insulin-like growth factor binding proteins
  • Insulin-like growth factor-I

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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