Association of the IGF-I promoter P1 polymorphism with risk of cervical cancer

Human papillomaviruses (HPV16, HPV18, HPV31, HPV33) are etiological agents in the development of cervical cancer. HPVs infect epithelial cells and depend on epithelial differentiation for the completion of their life cycle. Insulin-like growth factor I (IGF-I) is a potent mitogen involved in the regulation of cell proliferation and apoptosis of many cell types including normal and transformed epithelial cells. Deregulation of IGF-I expression and action is linked to diverse pathologies including cancer. A polymorphism in the P1 promoter region of the IGF-I gene may directly influence its expression. Using the PCR-SSCP method and sequencing of DNA, we identified a single nucleotide polymorphism (SNP) at -383(C>T) position of promoter P1 of the IGF-I in 16% of the study HPV-positive women with precancerous and cancerous lesions. In vitro, we observed that the SNP at-383(C>T) site significantly increased the reporter gene expresion in the HepG2 cell line, but not in the HeLa cell line relative to the wild type promoter. It suggests that the studied SNP can change expression of the IGF-I gene in distinct ways in different types of tissues. Deregulation of expression of the IGF-I gene can affect normal epithelium development and in case of HPV infection can potentially disrupt the virus life cycle and stimulate its passage into the oncogenic life cycle or persistent viral infections. Therefore, we propose that SNP C>T at the -383 position of P1 promoter may be one of the helpful prognostic markers in the diagnosis of cervical cancer development of women with persistent infection in the ectocervical epithelium. We have not found any association between the polymorphism CA repeats in the promoter P1 region of the IGF-I gene and suceptibility to HPV infection and cervical cancer development. The (CA)19 allele was the most common in the study of this group of women.