Tumor Biology

, Volume 34, Issue 2, pp 953–961

VCP gene variation predicts outcome of advanced non-small-cell lung cancer platinum-based chemotherapy

  • J. Peng
  • L. X. Yang
  • X. Y. Zhao
  • Z. Q. Gao
  • J. Yang
  • W. T. Wu
  • H. J. Wang
  • J. C. Wang
  • J. Qian
  • H. Y. Chen
  • L. Jin
  • C. X. Bai
  • B. H. Han
  • W. M. Wang
  • D. R. Lu
Research Article

Abstract

Valosin-containing protein (VCP), or p97, is a member of the ATP-binding protein family, and is involved in numerous cellular events, such as, protein degradation, membrane fusion, and chaperone activity. VCP has been demonstrated playing a critical role in non-small-cell lung cancer (NSCLC) pathogenesis and progression recently. We investigated the association between VCP polymorphisms and clinical outcome in advanced NSCLC patients undergoing platinum-based chemotherapy. We recruited 663 Chinese advanced NSCLC patients who were treated with platinum-based regimens, and using their clinical data, we assessed the efficacy and side effects of their treatment. Three tag-single nucleotide polymorphisms (SNPs) of VCP were genotyped. SNP rs2074549 showed a significant association with severe neutropenia. Its G/G genotype increased the risk of grade 3 or 4 neutropenia compared with wild-type homozygotes A/A (P = .001, odds ratio = 2.975). Haplotype association analysis revealed that CGA was associated with the increased incidence of severe neutropenia (P = .041, odds ratio = 1.439). However, no significant relationship was found between the presence of VCP polymorphisms and treatment efficacy when objective response, progression-free survival, and overall survival (OS) were evaluated. Our study is the first to provide evidence that VCP polymorphisms are associated with a severe chemotherapy-related adverse outcome in platinum-treated advanced NSCLC patients.

Keywords

Non-small cell lung cancer Platinum-based chemotherapy Pharmacogenetics Single nucleotide polymorphism Valosin containing protein 

Abbreviations

CI

confidence interval

CR

complete response

HR

hazard ratios

LD

linkage disequilibrium

NSCLC

non-small-cell lung cancer

OR

odds ratios

OS

overall survival

PD

progressive disease

PFS

progression-free survival

PR

partial response

PS

performance stage

SD

stable disease

SNPs

single nucleotide polymorphisms

TNM

tumor–node–metastasis

VCP

valosin-containing protein

Supplementary material

13277_2012_631_MOESM1_ESM.pdf (129 kb)
ESM 1(PDF 129 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • J. Peng
    • 1
  • L. X. Yang
    • 2
  • X. Y. Zhao
    • 1
  • Z. Q. Gao
    • 3
  • J. Yang
    • 4
  • W. T. Wu
    • 1
  • H. J. Wang
    • 1
  • J. C. Wang
    • 1
  • J. Qian
    • 1
  • H. Y. Chen
    • 1
  • L. Jin
    • 1
  • C. X. Bai
    • 5
  • B. H. Han
    • 2
  • W. M. Wang
    • 6
  • D. R. Lu
    • 1
  1. 1.State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life SciencesFudan UniversityShanghaiChina
  2. 2.Department of Cardiothoracic Surgery, Changhai Hospital of ShanghaiSecond Military Medical UniversityShanghaiChina
  3. 3.Department of Respiratory Disease, Shanghai Chest HospitalShanghai Jiaotong UniversityShanghaiChina
  4. 4.Department of Toxicology, School of Public HealthHangzhou Normal UniversityHangzhouChina
  5. 5.Department of Pulmonary Medicine, Zhongshan HospitalFudan UniversityShanghaiChina
  6. 6.Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine Technique, College of Life SciencesChina Jiliang UniversityHangzhouChina

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