Role of Genetic Variant in the promoter region of hTERT gene and its association towards Lung Cancer pathogenesis

Abstract

Background: Cancer is fundamentally a genetic age-related disease that only appears when normal cells start to amass genomic instability and develop the ability to proliferate indefinitely. In genomic rearrangements that might cause chromosomal instability and cancer, telomere attrition during subsequent cell divisions is essential. Cancer cells need telomeres, which are repetitive (TTAGGG) DNA–protein complexes located at the ends of chromosomes, to survive. Primary cells have a finite number of divisions possible. This restriction is also known as the Hayflick restriction. In most eukaryotes, the ribonucleoprotein complex telomerase is required for the upkeep of linear chromosomes. It consists of a long non-coding RNA that contains the reverse transcriptase catalytic subunit and the template sequence needed to generate telomeres. The two main components of telomerase are human telomerase reverse transcriptase (hTERT), a catalytic subunit with reverse transcriptase activity, and human telomerase RNA component (hTR), an RNA component that serves as a template for telomere lengthening. Purpose: We aim to investigate the Role of Genetic Variants in the promoter region of hTERT gene and its association towards Lung Cancer pathogenesis in the North Indian Population. Experimental Design: The study was performed on 387 cases and 384 controls, all receiving platinum-based chemotherapy, and the hTERT polymorphism is being investigated by PCR for potential links to lung cancer risk. Following conducting this association analysis, 95% confidence intervals (CIs) and the adjusted odds ratio (AOR) were obtained using logistic regression. The adjusted hazard ratio was determined by Cox regression analysis, and the univariate Kaplan-Meier approach was utilised to assess the overall survival of lung cancer patients. A p-value of < 0.5 was considered statistically significant in all analyses