The Roles of EXO1 and RPA1 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy

Abstract

Background. Lung cancer is one of the major causes of cancer-related mortality worldwide. DNA repair and damage response contribute to genomic instability that accompanies tumor progression. In this study, we focus on evaluating association between DNA repair polymorphisms of EXO1, RPA1, and prognosis in lung cancer patients whom received platinum-based chemotherapy. Methods. 593 lung cancer patients were recruited in this study. We performed genotyping of 19 single nucleotide polymorphisms (SNPs) by Sequenom MassARRAY. Cox regression analysis was used to assess overall survival (OS) and progression-free survival (PFS) among SNP genotypes. Results. Significant differences in PFS and OS were observed in RPA1 rs5030740, EXO1 rs1776148, and rs1047840. Results showed that patients with CC genotype in rs5030740 (recessive model: $P=0.034$ ) had a better PFS. Patients with AA or/and AG genotypes in rs1776148 (additive model: $P=0.004$ ; dominant model: $P=0.048$ ) and AA genotype in rs1047840 (recessive model: $P=0.023$ ) had longer OS. We also demonstrated differences in subgroup analysis between rs5030740, rs1776148, rs1047840, and prognosis. Conclusions. Our results indicated that EXO1 rs1776148, rs1047840, and RPA1 rs5030740 were significantly associated with prognosis of lung cancer. Rs1776148, rs1047840, and rs5030740 may act as prognosis markers in lung cancer patients with platinum-based chemotherapy.