Abstract

INDIVIDUAL VARIATION IN p53 RESPONSIVENESS: A PHARMACOGENOMIC APPROACH

Anusooya N J, Krishnapriya A S, Deepak O M, Aparna G Nair, Krishnan Namboori P K*

ABSTRACT

Background: The TP53 gene encoding for tumor suppressor protein p53 in cancer has been studied to identify the individual variations in p53 responsiveness. The investigation includes heredity factor analysis, gene-gene interaction study and gene-environment factor analysis. Methodology: The above gene has been explored to identify the functional effect of Single Nucleotide Polymorphisms (SNPs). 1005 SNPs have been recognized in the TP53 gene, out of which 477 were in the coding non-synonymous and the remaining in the UTR region. During the analysis, 15 SNPs have been predicted as damaging. The native and the mutant protein structures of the damaging SNPs were analyzed. In the gene-environment factor analysis, the effect of nicotine on TP53 mutation corresponding to the SNPs, A/G or G/A has been studied from the Denmark and Indian populations, which has been reported as most susceptible for the effect. Results: For the TP53 gene, nine mutations have been identified as the most deleterious and responsible for cancer. In the gene-gene interaction study, TAF1 and TP53 genes are found to be most correlated. Moreover, 44% of the overlapping genes are involved in HIV life cycle. Conclusion: It can be concluded that there is high proneness of cancer patients to acquire HIV and vice versa. Also, individuals possessing the habit of chewing tobacco and smoking cigarettes have higher rate of deleterious mutations responsible for cancer. Most interestingly, women are found to be more prone to the disease than men from the above groups.

Keywords: p53, Cancer, gene.