IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC).
Rinaldi S., Peeters PH., Berrino F., Dossus L., Biessy C., Olsen A., Tjonneland A., Overvad K., Clavel-Chapelon F., Boutron-Ruault MC., Téhard B., Nagel G., Linseisen J., Boeing H., Lahmann PH., Trichopoulou A., Trichopoulos D., Koliva M., Palli D., Panico S., Tumino R., Sacerdote C., van Gils CH., van Noord P., Grobbee DE., Bueno-de-Mesquita HB., Gonzalez CA., Agudo A., Chirlaque MD., Barricarte A., Larrañaga N., Quiros JR., Bingham S., Khaw KT., Key T., Allen NE., Lukanova A., Slimani N., Saracci R., Riboli E., Kaaks R.
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.