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Journal of Cancer Research and Clinical Oncology

Published in:

01-09-2012 | Original Paper

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

Authors: L. Knez, M. Košnik, T. Ovčariček, A. Sadikov, E. Sodja, I. Kern, T. Cufer

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2012

Abstract

Purpose

Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes.

Patients and methods

This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin–etoposide or cyclophosphamide–epirubicin–vincristine chemotherapy. To determine the ABCB1 genotype, allelic specific TaqMan^® probes were used in a RT-PCR .

Results

Patients carrying the G2677T/A TT + TA + AA genotypes (24 %) or the C3435T CT + TT genotypes (72 %) or the 2677T/A-3435T haplotype (40 %) had a longer PFS (Cox regression, P = 0.052, 0.037 and 0.037, respectively); these associations persisted also in multivariate analyses (Cox regression, P = 0.028, 0.037 and 0.030, respectively). Moreover, patients with the C3435T CT + TT genotypes had a longer OS both in univariate and multivariate analysis (Cox regression, P = 0.022 and 0.028, respectively). A trend toward longer OS was noted for the 2677T/A-3435T haplotype (Cox regression, P = 0.051), but its independent value was not confirmed (Cox regression, P = 0.071).

Conclusions

Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation.

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Title: Predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype in small cell lung cancer patients treated with chemotherapy
Authors: L. Knez
M. Košnik
T. Ovčariček
A. Sadikov
E. Sodja
I. Kern
T. Cufer
Publication date: 01-09-2012
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 9/2012
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-012-1231-1

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Abstract

Purpose

Patients and methods

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Conclusions

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