Abstract
Background: TP53 is one of the most important tumor suppressor genes, regulating various cellular processes and playing a pivotal role in preventing a cell to become malignant. P53 mutant protein containing arginine or proline at codon 72 shows different biological and biochemical activity. So, the aim of the present study was to find out the role of mutated P53 gene with different codon 72 variants on the clinical outcome of patients suffering from NSCLC. Materials and methods: A case control study of 100 NSCLC patients and 100 cancer free healthy controls was performed. TP53 codon 72 polymorphism and mutations at exon 5 and 8 were analyzed in NSCLC patients using AS–PCR and survival curves were plotted using Kaplan–Meier analysis. Results: A statistically significant difference was observed in the frequencies of P53 codon 72 variants between cases and healthy controls (p<0.003) with a strong association of risk of developing NSCLC with homozygous Pro/ Pro genotype, OR 5.3 ( 95% CI 1.8-15.3, p<0.001).TP53 mutations at exon 5/8 occurred in 78% of the cases and Pro/Pro genotype of codon 72 was associated with increased number of P53 mutations, OR 4.7(95% CI 0.5-44.8): Pro/Pro homozygotes,16 of 17 (94.1%); Arg/Pro heterozygotes, 45 of 61 (73.8%); and Arg/Arg homozygotes, 17 of 22 (77.3%). Codon 72 Pro/Pro homozygotes were associated with poor overall survival and the Pro/Pro genotypes with P53 mutations also predicted decreased overall survival .The median survival time for patients with wild type P53 and mutated P53 with Arg/Arg and Pro/Pro codon 72 genotypes were 14.5, 11.5 and 4.0 months respectively (p=0.003). Conclusion: Pro/Pro variant of P53 codon 72 was associated with increased number of P53 mutations, and was associated with adverse clinical outcome of NSCLC patients of north India.
Highlights
Lung cancer is the most commonly diagnosed cancer worldwide, 1.61 million, 12.7% of the total and is the leading causes of cancer deaths, 1.38 million, and 18.2% of the total [1]
A statistically significant difference was observed in the frequencies of P53 codon 72 variants between cases and healthy controls (p
Pro/Pro variant of P53 codon 72 was associated with increased number of P53 mutations, and was associated with adverse clinical outcome of NSCLC patients of north India
Summary
Lung cancer is the most commonly diagnosed cancer worldwide, 1.61 million, 12.7% of the total and is the leading causes of cancer deaths, 1.38 million, and 18.2% of the total [1]. Cancer mortality rates varied greatly in different states, including lung cancer the most common cancer in men in cities like Calcutta, Mumbai and New Delhi, accounting more than 11% in men, aged 30–69 years [3]. Human TP53 gene located in chromosome 17p13.1, encoded by 20 kb gene contains 11 exons and 10 introns, encodes approximately 53 kDa protein of 393 amino acids, plays its anti-cancer role in several mechanisms such as DNA repair, cell cycle arrest and apoptosis etc [4]. The aim of the present study was to find out the role of mutated P53 gene with different codon 72 variants on the clinical outcome of patients suffering from NSCLC
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