Effects of polymorphisms in the XRCC1, XRCC3, and XPG genes on clinical outcomes of platinum-based chemotherapy for treatment of non-small cell lung cancer

Abstract

ABSTRACT. This study aimed to investigate the effects of singlenucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the outcomes of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The study period was from January 2005 to January 2006, and 378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC. Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction combined with a restriction fragment length polymorphism assay was used for genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability of responding well to platinum-based chemotherapy, indicated by an odds ratio (OR) of 2.27 [95% confidence interval (CI) = 1.64-6.97]. Similarly, the XPG T/T genotype was significantly associated with improved responses to chemotherapy, indicated by an OR of 1.90 (95%CI = 1.10-3.28). The XRCC1 399A/A genotype was significantly associated with longer disease-free survival and overall survival, indicated by hazard ratios (HRs) of 0.48 (95%CI = 0.25-0.88) and 0.51 (95%CI = 0.26-0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of longer disease-free survival and overall survival of NSCLC patients treated with platinum-based chemotherapy (HR = 0.47; 95%CI = 0.22-0.82 and HR = 0.52; 95%CI = 0.31-0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His might significantly affect the clinical outcomes of platinum-based chemotherapy, highlighting the need for larger studies to confirm the role of these two SNPs in outcomes of NSCLC treatments.

Genetic Polymorphisms and Platinum-based Chemotherapy Treatment Outcomes in Patients with Non-Small Cell Lung Cancer: A Genetic Epidemiology Study Based Meta-analysis

“…(2014)Asian (China)187124/63NRIIIA-IVPlatinum-basedOR, OSMALDI-TOF-MS ERCC1 rs11615 rs3212986, rs2298881 99 Zhang, L. (2014)Asian (China)375249/126NRIIIA-IVCBP+NVP+DDP, DDP+DOCOR, OS, PFSSequenom MassARRAY platform XPD rs13181 rs1799793 rs1052555 rs238406, XRCC1 rs25487 rs1799782 100 Jin, Z. Y. (2014)Asian (China)378297/8162.4 (36–78)I-IVDDP+GEM/DOC/NVP/TAXOR, OSPCR-RFLP XPG rs1047768 rs17655 XRCC1 rs25489, XRCC3 rs861539 101 Hu, W. (2014)Asian (China)277184/9363.1 (29–75)IIIA-IVPlatinum-basedOS, PFSPCR-RFLP XPG rs1047768 rs17655 rs2296147 rs873601 102 Peng, Y. (2014)Asian (China)235180/5558 (29–84)IIIA-IVDDP+TAX/DOC/GEMOR, OSPCR-CTTP XRCC1 rs25487 103 Zhou, M. (2014)Asian (China)9356/3761.5 (NR)IIIB-IVDDP+GEMORPCR-RFLP XPD rs13181 rs1799793, CDA rs2072671 104 Zhao, X.…”

Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

“…Patients of XRCC1 C580T CT and TT carriers had better response than CC carriers. Meta-analysis of XRCC3 C18067T included 6 studies [7, 22, 36, 39, 41, 42]. There was no heterogeneity across these studies ( P = 0.427, I 2 = 0%), thus we chose fixed-effect model.…”

“…Patients carrying CC genotype of MDR1 C3435T or GG genotype of MDR1 G2677T/A had better chemotherapy response. There were 11 publications studied association of XRCC1 G1196A [7, 22, 36–40, 46, 50–52], but high heterogeneity ( P <0.001, I 2 = 74.3%) and publication bias exist among the studies (Begg's test P = 0.024; Egger's test P = 0.002). Moreover, it was hardy to determine about the association of XPD A2251C with chemotherapy response for its 95%CI was 0.99-1.44.…”

XRCC1 rs1799782 polymorphism and objective response rate in NSCLC patients treated with platinum-based chemotherapy

“…Wang et al suggested that Chinese Han people with rs1799782 TT/CT genotype of XRCC1 gene may have increased risk of developing colorectal cancer [8]. Some previous studies suggested that XRCC1 rs1799782 polymorphism was associated with the objective response rate (ORR) of platinum-based chemotherapy [9][10][11][12][13][14][15][16][17][18][19][20][21]. However, the results were not coincident.…”