Aim:Lung cancer is considered to be the most common cancer in the world. In humans, about 50% or more cancers have a mutated tumor suppressor p53 gene thereby resulting in accumulation of p53 protein and losing its function to activate the target genes that regulate the cell cycle and apoptosis. Extensive research conducted in murine cancer models with activated p53, loss of p53, or p53 missense mutations have facilitated researchers to understand the role of this key protein. Our study was aimed to evaluate the frequency of cytosine deletion in nonsmall cell lung cancer (NSCLC) patients.Methods:One hundred NSCLC patients were genotyped for P53 (exon5, codon168) cytosine deletion leading to loss of its function and activate the target genes by allele-specific polymerase chain reaction. The P53 cytosine deletion was correlated with all the clinicopathological parameters of the patients.Results and Analysis:59% cases were carrying P53 cytosine deletion. Similarly, the significantly higher incidence of cytosine deletion was reported in current smokers (75%) in comparison to exsmoker and nonsmoker. Significantly higher frequency of cytosine deletion was reported in adenocarcinoma (68.08%) than squamous cell carcinoma (52.83%). Also, a significant difference was reported between p53 cytosine deletion and metastasis (64.28%). Further, the majority of the cases assessed for response carrying P53 cytosine deletion were found to show faster disease progression.Conclusion:The data suggests that there is a significant association of the P53 exon 5 deletion of cytosine in codon 168 with metastasis and staging of the disease.

Background: p53 plays a central role in protecting the integrity of the genome. Its activity is ubiquitously lost in cancers, either by inactivation of its protein (p53 pathway) or by mutation in the p53 gene, thereby indicating its importance in understanding cancer and as a therapeutic target. Given the high frequency of the hotspot R282W p53 gene mutation in our NSCLC patients, we have evaluated the association of R282W mutation with the progression of the malignancy.Methods: Blood DNA was extracted from cases. The R282W hotspot p53 gene mutation was detected by using ASO-PCR. Most of the NSCLC patient's submitted samples for EGFR gene mutation analysis. Results:The clinical significance of R282W hotspot p53 gene mutation in exon 8, codon 268 (C>T) was studied in hundred clinically confirmed NSCLC patients samples. Sixty two of hundred (62%) cases were reported positive for R282W p53 mutation. The clinically significant difference was reported between early and the advanced stages (72% vs. 43%) (p<0.007). Similarly higher frequency of this mutation was reported in adenocarcinoma (76.08%) than squamous cell carcinoma 27 (50%) (p<0.0134). Significantly higher frequency of R282W p53 mutation was reported in distant metastasis 23 (85.18%) than the metastasis (<0.0075), current smokers than the ex smokers (p=0.02).These findings suggest that stage, smoking, histological type, metastasis is strongly associated with the incidence of R282W mutation. Other variables as gender, age, smoking level, and family history of any cancer does not showing any significant association with p53, R282W mutation. Slightly lower overall survival was reported in NSCLC patients with R282W mutation than wild p53 cases (p<0.049). Conclusion:Our results suggest that the hotspot R282W p53 mutation may influence the susceptibility, progression of NSCLC patients in Indian population. Large population-based prospective studies are required to validate our findings.

Background: MDM2 is an important negative regulator of the TP53 pathway, over expressed in many cancers as oncoprotein. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus play an important role in carcinogenesis. Aim and methods:To test our hypothesis that the MDM2 promoter polymorphisms are associated with risk of non small cell lung cancer, we conducted a hospital-based, case-control study of 136 Indian patients diagnosed with NSCLC and 136 cancer-free controls and investigated the association between genetic variation in the promoter region of MDM2 (c.-51309G4T, rs2279744:g.G4T) and the risk of developing NSCLC by tetra-primer ARMS-PCR and ASO-PCR.Results: Compared with the MDM2-2580TT genotype, we found that the MDM2-309G variant genotypes were associated with an increased risk of NSCLC in Indian patients [

Background: Apoptotic inhibitor gene survivin regulates apoptosis and cell cycle progression. Functional polymorphism in the promoter region of survivin influences its expression may lead to the development of several cancers including lung cancer. Our study aimed to investigate the association of survivin-31G>C polymorphism with the risk of NSCLC in Indian population.Methods: A hospit al-based case control study of 136 cases and 136 age-gender matched healthy controls was performed by PCR-RFLP.Results: Our findings reveal that a statistically increased risk and poor survival was associated with the BIRC5 -31CC genotype (OR 3.13, 95% CI 1.57-6.25) compared to the genotype containing G allele GC (OR 1.22, 95% CI 0.69-2.14). In addition significant association was found with stage and distant metastasis status of NSCLC patients. Conclusions:Our results conclude that the function polymorphism (-31G>C) in the promoter of survivin gene is associated with risk and susceptibility to NSCLC.