Polymorphism in XRCC1 gene modulates survival and clinical outcomes of advanced North Indian lung cancer patients treated with platinum-based doublet chemotherapy.

Abstract

Survival in lung cancer patients is genetically determined. Single nucleotide polymorphisms (SNPs) in DNA repair genes are observed to play a critical role in survival as DNA repair itself can behave as double-edged sword. We aim to explore the association of DNA repair gene XRCC1 in survival and clinical outcomes for North Indian population. Blood sample from patients diagnosed with lung cancer was taken. DNA isolation and genotyping were performed for the SNPs of XRCC1 gene. Further, patients were followed up through telephonic conversation after every 2months for 3years. Statistical analysis was carried out using Kaplan-Meier to determine the median survival time (MST) and Cox proportional regression model to determine the hazards ratio. Further, logistic regression was used to calculate to calculate the objective response. The mutant genotype for XRCC1 399 is observed to have a better survival (MST=9.6). Histological stratification did not reveal any association for any SNP except for SCLC subtype in XRCC1 632 with an increased death rate (HR 3.08, p=0.02). On stratification according to chemotherapy regimen administered; cisplatin/carboplatin+docetaxel was observed to increase survival for XRCC1 399 mutant genotype (AA) (HR 0.26, p=0.05). Cisplatin/carboplatin+irinotecan increased survival in both heterozygotes (GA) and combined variants (GA+AA) (HR 0.22, p=0.014; HR 0.23, p=0.012). The polymorphic variants within the XRCC1 gene have found to play an important role in overall survival of lung cancer patients undergoing specific chemotherapy regimen.