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

Oncotarget. 2016 Aug 23;7(34):55741-55756. doi: 10.18632/oncotarget.9688.

Abstract

Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/ C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients.

Keywords: NSCLC; chemotherapy response; meta-analysis; platinum; polymorphism.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • Female
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Pharmacogenetics*
  • Platinum / therapeutic use
  • Polymorphism, Single Nucleotide
  • X-ray Repair Cross Complementing Protein 1 / genetics

Substances

  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • X-ray repair cross complementing protein 3
  • XRCC1 protein, human
  • Platinum