Association of p53 codon 72 polymorphism and survival of North Indian lung cancer patients treated with platinum-based chemotherapy.
p53 helps in maintaining genomic stability by undergoing cellular arrest, DNA repair or cellular apoptosis during DNA damage. So, as to find the association of p53Arg72Pro towards lung carcinogenesis and overall survival of North Indian lung cancer patients, single nucleotide polymorphic variant (rs1042522) was analyzed. 840 subjects including 420 cases and 420 controls were recruited and genotyped using PCR-RFLP technique for p53Arg72Pro polymorphic site. Association was analyzed using adjusted odds ratio along with its confidence intervals (95 % CI) and p value predicted from logistic regression whereas overall survival for lung cancer patients was obtained using Kaplan-Meir and Cox regression model for different parameters to obtain hazard ratio and survival time with statistical significance (log-rank p value). None of the variant genotypes for p53Arg72Pro showed any association towards lung cancer risk or any specific histological subtype. Lung cancer subjects with Pro/Pro genotype had better median survival time as compared to Arg/Pro genotype (10 months; HR = 0.65; 95 % CI = 0.45-0.95; p = 0.03). Furthermore, female lung cancer patients with Arg/Pro (HR = 0.08; 95 % CI = 0.02-0.34; p = 0.0005) and Pro/Pro (HR = 0.21; 95 % CI = 0.06-0.67; p = 0.008) genotypes showed a better overall survival and hence a better prognosis as compared to males. Our data also reveals that lung cancer patients with ECOG scores between 0 and 1 and carrying the Pro/Pro had better chances of survival. p53 codon 72 polymorphism could play a role as a prognostic marker in lung cancer patients.
Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India.
Ankita
A
Kumari
Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India.
Charu
C
Bahl
Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Sector 14, Chandigarh, India.
Navneet
N
Singh
Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Sector 14, Chandigarh, India.
Digambar
D
Behera
Department of Biotechnology, Thapar University, Patiala, Punjab, 147002, India. siddharthsharma.phd@thapar.edu.
Siddharth
S
Sharma
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D003062:Codon; D019008:Drug Resistance, Neoplasm; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
D000970:Antineoplastic Agents; D003062:Codon; D017671:Platinum Compounds; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
Genotype; Lung cancer; Polymorphisms; Survival; p53 codon 72