Identification of novel heterozygous Apex 1 gene variant (Glu87Gln) in patients with head and neck cancer of Indian origin.

Gene polymorphism among humans is one of the factors governing individual's susceptibility and resistance to various diseases including cancer. DNA repair enzymes play an important role in protecting our genome from various mutagens and preventing cancer. The role of DNA repair enzyme Apurinic/Apyrimidinic endodeoxyribonuclease 1 (Apex 1) in cancer has been very well documented. Using genomic DNA, Apex 1 coding region of 76 patients (n = 76) with head and neck cancer were amplified and sequenced to detect variations in the sequence. Of 76 patients, 1 patient with heterozygous novel Apex 1 variant (Glu87Gln) was identified. A comparative analysis of wild type and variant protein using in silico approach was performed to understand the difference in the structure and the function. This further revealed that the variant had a slight impact on the structure, which affected the stability and function of the protein. Using the state-of-the-art Molecular dynamic simulation analysis, we observed a loss in number of hydrogen bonds and salt bridge with a substitution of Gln for Glu at Position 87. This could be a possible reason behind the loss of stability/function of the protein. This study revealed a new variant of the Apex 1 gene; further studies will lead to the novel roles played by the variant Apex 1 protein in cause, disease progression, and response to the treatment in patients with cancer with Glu87Gln variant.