Affiliations: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Uttar Pradesh, India
Correspondence:
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Corresponding author: Dr. Rama Devi Mittal, Department of Urology, SGPGIMS, Raebareli Road, Lucknow-226014, India. Tel.: +91 522 2668004 8, Ext. 4116; Fax: +91 522 -2668 017; E-mail: ramamittal@gmail.com; rmittal@sgpgi.ac.in.
Abstract: p53 is a major orchestrator of cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, etc. A few polymorphic sites, one at codon72 of exon4, intron3 16bpdel/ins, intron6G>A have been studied with regard to Bladder cancer (BC) risk in North Indians. Genotypes were assessed in hospital-based case-control study comprising of 200BC cases, 265healthy controls. After extraction of genomic DNA from blood, genotyping was done using PCR Restriction Fragment Length Polymorphism. Individuals with p53R72P G>C, CC genotype demonstrated marginally reduced risk of BC (p=0.053, OR=0.29, 95%CI = 0.08–1.02). In intron3 16bp-ins/del, I allele, its carrier (D/I+I/I) were at higher risk (p = 0.012, OR = 1.52, 95%CI = 1.09-2.11; p = 0.040, OR = 1.55, 95%CI = 1.02–2.38). Haplotypes p53 intron6 G-R72P G-intron3 I (GGI) and p53 intron6 A-R72P G-intron3 D (AGD) (p < 0.001, Pc= 0.008, OR= 2.44, 95%CI =1.52–3.93; p = 0.006, Pc= 0.048, OR = 1.89, 95%CI = 1.20–2.98 respectively), were also found to be associated with increased risk. intron6G>A, intron3 16bp ins/del gene-combination (GG-I/D, GA-I/I) showed significant association with BC. In R72P G>C, GC was associated with reduced risk of recurrence (HR = 0.29, p = 0.022, 95%CI = 0.11–0.84) in patients receiving BCG treatment thus showing increased recurrence-free survival(GC/GG = 49/30months;log rank = 0.008). p53R72PG>C, intron3-16bp duplication polymorphism are potentially important, clinically relevant genetic markers contributing to BC susceptibility. Kaplan-Meier analysis of BC patients harboring the R72P GC showed significantly longer recurrence free survival with adjuvant immunotherapy.
