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Predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype in small cell lung cancer patients

L Knez1, M Košnik, T Ovčariček

  • 1University Hospital Golnik, Golnik 36, 4204, Golnik, Slovenia. lea.knez@klinika-golnik.si

Journal of Cancer Research and Clinical Oncology
|May 1, 2012
PubMed
Abstract

Insights

Certain gene variations in the ATP-binding cassette transporter B1 (ABCB1) may predict longer survival for small cell lung cancer (SCLC) patients undergoing chemotherapy. Further validation is needed for clinical use.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Drug resistance significantly impacts small cell lung cancer (SCLC) treatment efficacy.
  • The ATP-binding cassette transporter B1 (ABCB1) protein plays a crucial role in multidrug resistance.
  • Genetic variations in ABCB1 may influence patient response to chemotherapy.

Purpose of the Study:

  • To investigate the association between ABCB1 gene polymorphisms (G2677T/A, C3435T) and their haplotype with progression-free survival (PFS) and overall survival (OS) in SCLC patients.
  • To assess the predictive value of these ABCB1 variations in patients treated with standard chemotherapy regimens.

Main Methods:

  • Genotyping of ABCB1 polymorphisms G2677T/A and C3435T using allelic specific TaqMan probes via RT-PCR.
  • Survival analysis (PFS and OS) using Cox regression models in 177 SCLC patients.
  • Multivariate analyses were performed to confirm the independent value of identified associations.

Main Results:

  • Patients with specific genotypes (G2677T/A TT+TA+AA or C3435T CT+TT) and the 2677T/A-3435T haplotype showed significantly longer PFS.
  • The C3435T CT+TT genotypes were associated with longer OS in both univariate and multivariate analyses.
  • A trend towards longer OS was observed for the 2677T/A-3435T haplotype, though not independently confirmed.

Conclusions:

  • ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype may have predictive value for improved PFS and OS in Caucasian SCLC patients receiving chemotherapy.
  • These findings suggest a potential role for pharmacogenetics in tailoring SCLC treatment.
  • Further validation studies are necessary before clinical implementation of ABCB1 genotyping for SCLC treatment decisions.

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