Single-nucleotide polymorphisms of nucleotide excision repair genes and their association with overall survival in North Indian lung cancer patients treated with platinum-based doublet chemotherapy.

Abstract

The aim of the study is to understand the association of Nucleotide excision repair (NER) inter-genetic polymorphic combinations with overall survival (OS) in lung cancer as well as its histological subtypes in the North Indian population. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. For survival analysis, the univariate Kaplan-Meier and multivariate Cox regression model were applied. Recursive partitioning method, survival analysis tree was applied to study unfavorable genotypic combinations in NER single-nucleotide polymorphisms. Combinatorial studies suggested no association between polymorphic combinations of NER genes and OS in lung cancer patients. When stratified as per lung cancer histological subtypes, adenocarcinomas patients with XPG 670 and XPC 499 polymorphism a significant increase in OS in combined heterozygous and mutant genotype with a lower hazardous ratio (Hazard Ratio1 (HR) = 0.20; P = 0.004). Small-cell lung carcinoma (SCLC) patients with XPF 11985A>G and XPD Arg156Arg polymorphism showed a 4-fold hazard ratio among heterozygous genotype (HR1 = 4.84; P = 0.007) where no significant results are obtained in patients suffering from squamous cell carcinoma histological subtypes. STREE showed XPG Asp1104His (W), XPD Lys751Gln (H + M), XPF Arg415Gln (H + M) genotype was associated with a lower hazard ratio (P = 0.0007) showing survival of 11.6 months when compared with the reference (median survival time = 3.52). It can be concluded that SCLC patients with polymorphic combinations of the NER pathway were associated with a higher risk of mortality. STREE depicted the association of NER polymorphic combinations with a lower hazard ratio predicting them to be a good prognostic factor for lung cancer.