The Role of BIRC5 Polymorphisms in Squamous Cell Carcinoma of Head and Neck

Survivin, encoded by BIRC5 gene, belongs to the family of inhibitors of apoptosis (IAP) proteins. In healthy organisms it is not expressed in differentiated tissues, while its expression is markedly increased in tumors. BIRC5 polymorphisms have been previously associated with increased expression, stability and localization of survivin, all of which can affect tumor development. In this study we investigated the role of BIRC5 polymorphisms in oral and oropharyngeal squamous cell carcinoma. Genetic testing of 38 patients and 74 healthy controls was conducted using high resolution melting analysis and Sanger sequencing. Results showed different significance of individual BIRC5 polymorphisms. c.-235G>A showed significantly higher frequency in patients compared to control samples. For c.-644T>C and c.-625G>C, minor homozygous genotypes were significantly associated with higher Broders’ grade, which was also observed for c.-235G>A. The minor homozygous genotypes of either c.9194G>A or c.9809T>C were associated with higher TNM stage. For c.-644T>C and c.-625G>C, the presence of minor allele was associated with higher survivin mRNA expression. Besides eight frequent, six rare polymorphisms were found, c.9349G>C found in 3’ UTR previously unpublished. This was the first study in Croatia which demonstrated correlation between BIRC5 polymorphisms with the level of survivin expression and the risk of oral and oropharyngeal squamous cell carcinoma. Since it is known that increased expression of survivin is associated with increased resistance to chemotherapy and radiation, as well with poorer survival, BIRC5 polymorphisms could be used as predictive and prognostic biomarkers in the etiology of head and neck squamous cell cancer.