A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy

Pharmacogenomics J. 2014 Feb;14(1):20-7. doi: 10.1038/tpj.2013.7. Epub 2013 Mar 12.

Abstract

We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) influencing overall survival (OS) of small-cell lung cancer (SCLC) patients. We prospectively collected blood samples from 139 SCLC patients who participated in phase II studies of irinotecan and cisplatin (IP) chemotherapy as first-line therapy. Among 334 127 SNPs, which passed quality control, seven showed significant association with OS. The rs16950650CT, rs7186128AG or GG, rs17574269AG, rs8020368CC, rs4655567CC, rs2166219TT or rs2018683TT showed shorter OS compared with control alleles. Among the seven SNPs, rs4655567, rs8020368 and rs2018683 were significantly associated with a resistant relapse (RR). In the multivariate analysis, rs8020368CC was significantly associated with higher risk of RR (odds ratio=16.7, P=0.007). In vitro and in silico analysis showed that SNPs in C14orf49 might be associated with epithelial-to-mesenchymal transition. This exploratory GWAS identified candidate SNPs that may be predictive of the clinical outcome of SCLC patients receiving IP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cisplatin / administration & dosage
  • Cisplatin / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Data Interpretation, Statistical
  • Disease-Free Survival
  • Female
  • Genome-Wide Association Study
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Prospective Studies
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / mortality

Substances

  • Irinotecan
  • Cisplatin
  • Camptothecin