In Silico Analysis of Single Nucleotide Plymorphisms of XPD Gene in Lung Cancer Patients

Abstract

Lung cancer is one the leading cause of cancer death in both men and women. 80-85% of the lung cancer is of non-small cell lung cancer (NSCLC) and rest is contributed by small cell lung cancer (SCLC). Genetic variation in DNA repair genes has been reported to affect the chemotherapeutic response among non-small cell lung cancer patients. XPD gene play an important role in Nucleotide Excision repair pathway respectively. In the present study, deleterious SNPs of XPD gene was predicted based on consensus prediction tools and then deleterious SNPs was analyzed by different computational tools to know their effects of structure and function of XPD protein. Nineteen out of 174 clinically relevant SNPs were commonly found to be deleterious by three prediction tools. Fourteen SNPs were present inside of protein domain and five were outside of protein coding region. Sixteen SNPs commonly found to decrease the stability of protein by two tools (I-mutant and MuPro). Seventeen SNPs were prediction to be disease related by Phd-SNP and SNP&GO. RMSD value of mutant model generated by considering change due to 19 SNPs was found to be in range of 0.970 to 0.979 representing not much protein structural variation. Hence, it is suggested that these 19 SNPs of XPD gene may be associated with cancer development.