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 journalArticle

Abstract

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
Volume108
Issue number2
DOIs
Publication statusPublished - Jan 10 2004

Fingerprint

Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
C-Peptide
Endometrial Neoplasms
Insulin-Like Growth Factor I
Hyperinsulinism
Odds Ratio
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor Binding Protein 3
Polycystic Ovary Syndrome
Sweden
Type 2 Diabetes Mellitus
Italy
Case-Control Studies
Life Style
Obesity
Prospective Studies
Confidence Intervals
Insulin

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lukanova, A., Zeleniuch-Jacquotte, A., Lundin, E., Micheli, A., Arslan, A. A., Rinaldi, S., ... Kaaks, R. (2004). Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. International Journal of Cancer, 108(2), 262-268. https://doi.org/10.1002/ijc.11544

Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. / Lukanova, Annekatrin; Zeleniuch-Jacquotte, Anne; Lundin, Eva; Micheli, Andrea; Arslan, Alan A.; Rinaldi, Sabina; Muti, Paola; Lenner, Per; Koenig, Karen L.; Biessy, Carine; Krogh, Vittorio; Riboli, Elio; Shore, Roy E.; Stattin, Par; Berrino, Franco; Hallmans, Göran; Toniolo, Paolo; Kaaks, Rudolf.

In: International Journal of Cancer, Vol. 108, No. 2, 10.01.2004, p. 262-268.

Research output: Contribution to journalArticle

Lukanova, A, Zeleniuch-Jacquotte, A, Lundin, E, Micheli, A, Arslan, AA, Rinaldi, S, Muti, P, Lenner, P, Koenig, KL, Biessy, C, Krogh, V, Riboli, E, Shore, RE, Stattin, P, Berrino, F, Hallmans, G, Toniolo, P & Kaaks, R 2004, 'Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer', International Journal of Cancer, vol. 108, no. 2, pp. 262-268. https://doi.org/10.1002/ijc.11544
Lukanova A, Zeleniuch-Jacquotte A, Lundin E, Micheli A, Arslan AA, Rinaldi S et al. Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. International Journal of Cancer. 2004 Jan 10;108(2):262-268. https://doi.org/10.1002/ijc.11544
Lukanova, Annekatrin ; Zeleniuch-Jacquotte, Anne ; Lundin, Eva ; Micheli, Andrea ; Arslan, Alan A. ; Rinaldi, Sabina ; Muti, Paola ; Lenner, Per ; Koenig, Karen L. ; Biessy, Carine ; Krogh, Vittorio ; Riboli, Elio ; Shore, Roy E. ; Stattin, Par ; Berrino, Franco ; Hallmans, Göran ; Toniolo, Paolo ; Kaaks, Rudolf. / Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer. In: International Journal of Cancer. 2004 ; Vol. 108, No. 2. pp. 262-268.
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