Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer.
OBJECTIVE
Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP).


METHODS
Hospital-based case-control study.


METHODS
In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects.


RESULTS
In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP.


CONCLUSIONS
These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.
Pazaitou-Panayiotou
Kalliopi
K
Department of Endocrinology-Endocrine Oncology, Theagenio Cancer Hospital, Thessaloniki, Greece.
Kelesidis
Theodore
T
Kelesidis
Iosif
I
Kaprara
Athina
A
Blakeman
Jennifer
J
Vainas
Iraklis
I
Mpousoulegas
Aris
A
Williams
Catherine J
CJ
Mantzoros
Christos
C
D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology*; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors
D002352:Carrier Proteins; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C051815:somatotropin-binding protein