Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer.
Insulin-like growth factor I (IGF-I) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-I is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-I for biological activity. To assess the availability of IGF-I for receptor binding, we determined serum levels of IGF-I and IGFBP-3 and IGF-I/IGFBP-3 ratios. In a case-control study, 150 women aged 38 to 75 years presenting with stage-I or -II breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-I serum concentrations, decreased IGFBP-3 levels and increased IGF-I/IGFBP-3 ratios. The IGF-I/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-I/IGFBP-3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF-I in the circulation of pre-menopausal women may contribute to the development of breast cancer.
Bruning
P F
PF
The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam.
Van Doorn
J
J
Bonfrèr
J M
JM
Van Noord
P A
PA
Korse
C M
CM
Linders
T C
TC
Hart
A A
AA
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D017697:Premenopause / Q000097:blood*; D012016:Reference Values; D012307:Risk Factors
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I