Association between a functional polymorphism (-1195T>C) in the IGFBP5 promoter and head and neck cancer risk.

Abstract

To the best of our knowledge, no studies to date have evaluated roles of insulin-like growth factor binding protein 5 (IGFBP5) polymorphisms in risk of squamous cell carcinoma of the head and neck (SCCHN). A hospital-based study of 1082 patients with SCCHN and 1120 cancer-free controls was performed to investigate associations between 2 functional polymorphisms, -1195T>C and -709G>C, in the IGFBP5 promoter region and SCCHN risk. We demonstrated that the transcription factor, activator protein 1 (AP-1), differentially bound to T or C variants at -1195 in the promoter to regulate the IGFBP5 promoter activity and that the C variant genotypes were associated with deferential risk of late-stage SCCHN, compared to the TT genotype, particularly for human papillomavirus (HPV)-unrelated sites (adjusted odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19-4.11 for CC vs TT). The IGFBP5 -1195T>C polymorphism is functional and may potentially be a biomarker for susceptibility to late-stage SCCHN.