Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

Abstract

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). Design: 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)Z0.2, P!0.01) and a direct association between GHBP and disease risk (ORZ3.3, 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.

Body Mass Index Is Associated with Gene Methylation in Estrogen Receptor–Positive Breast Tumors

“…The IGFBP6 gene codes for a protein that binds with high affinity to insulin-like growth factor-2 (IGF-II) (32), which plays a role in cellular proliferation, differentiation, and migration, and is regulated by the IGFBP6 protein (32). Expression of IGFBP6 may be associated with cancer incidence (32), with studies finding lower expression of the protein in the serum of breast cancer patients when compared to the serum of those with benign breast disease (33, 34). Our finding of hypermethylation of IGFBP6 in obese patients suggests that obesity may lead to reduced expression in breast tissue via gene methylation.…”

Role of the growth hormone–IGF-1 axis in cancer

“…Moreover, elevated serum GH-binding protein (derived from the GHR by cleavage, and a measure of GHR expression [68]) is associated with a threefold increase in breast cancer incidence [69]. Immunohistochemical assessment has also revealed GHR overexpression in melanoma [70] and prostate carcinoma [71].…”

MANAGEMENT OF ENDOCRINE DISEASE: GH therapy and cancer risk in hypopituitarism: what we know from human studies

“…A similar result was observed for IGFBP1 in this study. The study of postmenopausal women showed an inverse association between IGFBP3 and risk of breast cancer, while other IGFBPs (IGFBP1, IGFBP4, and IGFBP6) were not significantly associated with breast cancer risk (39). There are also studies that reported no association between IGFBP3 and risk of cancer, or positive association between them (40,41).…”