*Squamous cell carcinoma of the head and neck (SCCHN)*

A study found that a single nucleotide polymorphism (G to A) in the IGFBP7 promoter region was significantly associated with a reduced risk of SCCHN, when analyzed in a hospital-based case-control study of 1065 SCCHN patients and 1112 cancer-free control subjects. Upon analyzing reporter gene constructs, the G to A allelic change at -418 of the IGFBP7 promoter had increased promoter and DNA binding activity, suggesting increased IGFBP7 protein expression [119].

Although IGFBP7 has been shown to function as a tumor suppressor in a wide variety of cancers, a few studies suggest that IGFBP7 has an opposite effect, ie. promoting cancer growth. These cancers include the blood cancer, leukemia, and the brain cancer, glioblastoma.

### *Glioblastoma*

IGFBP7 is a selective biomarker of glioblastoma (GBM) vessels, strongly expressed in tumor endothelial cells and vascular basement membrane [120]. IGFBP7 was strongly expressed in GBM specimens but not nontumor brain tissue. Moreover, statistical analysis showed that expression of IGFBP7 correlated inversely with overall GBM survival rates. Inhibition of IGFBP7 expression using siRNA transfection in a glioma cell line inhibited cell growth [121]. Addition of IGFBP7 to cell culture medium stimulated cell proliferation. IGFBP7 also promoted glioma cell migration, through downregulation of AKT phosphorylation and enhanced ERK1/2 activation [121]. IGFBP7 expression in brain endothelial cells was found to be upregulated by secreted factors from GBM cells through TGF-1/ALK5/Smad2 signaling pathway, which has been implicated in angiogenesis [122].
