IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC)

S. Rinaldi, P. H M Peeters, F. Berrino, L. Dossus, C. Biessy, A. Olsen, A. Tjonneland, K. Overvad, F. Clavel-Chapelon, M. C. Boutron-Ruault, B. Téhard, G. Nagel, J. Linseisen, H. Boeing, P. H. Lahmann, A. Trichopoulou, D. Trichopoulos, M. Koliva, D. Palli, S. PanicoR. Tumino, C. Sacerdote, C. H. Van Gils, P. Van Noord, D. E. Grobbee, H. B. Bueno-De-Mesquita, C. A. Gonzalez, A. Agudo, M. D. Chirlaque, A. Barricarte, N. Larrañaga, J. R. Quiros, S. Bingham, K. T. Khaw, T. Key, N. E. Allen, A. Lukanova, N. Slimani, R. Saracci, E. Riboli, R. Kaaks

Research output: Contribution to journalArticlepeer-review

Abstract

Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.

Original languageEnglish
Pages (from-to)593-605
Number of pages13
JournalEndocrine-Related Cancer
Volume13
Issue number2
DOIs
Publication statusPublished - Jun 2006

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

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