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ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen

BACKGROUND: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim...

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Autores principales: Sensorn, Insee, Sukasem, Chonlaphat, Sirachainan, Ekaphop, Chamnanphon, Montri, Pasomsub, Ekawat, Trachu, Narumol, Supavilai, Porntip, Pinthong, Darawan, Wongwaisayawan, Sansanee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835128/
https://www.ncbi.nlm.nih.gov/pubmed/27110128
http://dx.doi.org/10.2147/OTT.S100905
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author Sensorn, Insee
Sukasem, Chonlaphat
Sirachainan, Ekaphop
Chamnanphon, Montri
Pasomsub, Ekawat
Trachu, Narumol
Supavilai, Porntip
Pinthong, Darawan
Wongwaisayawan, Sansanee
author_facet Sensorn, Insee
Sukasem, Chonlaphat
Sirachainan, Ekaphop
Chamnanphon, Montri
Pasomsub, Ekawat
Trachu, Narumol
Supavilai, Porntip
Pinthong, Darawan
Wongwaisayawan, Sansanee
author_sort Sensorn, Insee
collection PubMed
description BACKGROUND: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim of this study is to investigate the impact of CYP3A5, CYP2D6, ABCB1, and ABCC2 polymorphisms on the risk of all distant and organ-specific metastases in Thai patients who received tamoxifen adjuvant therapy. METHODS: Genomic DNA was extracted from blood samples of 73 patients with breast cancer who received tamoxifen adjuvant therapy. CYP3A5 (6986A>G), CYP2D6 (100C>T), ABCB1 (3435C>T), and ABCC2 (−24C>T) were genotyped using allelic discrimination real-time polymerase chain reaction assays. The impacts of prognostic clinical factors and genetic variants on disease-free survival were analyzed using the Kaplan–Meier method and Cox regression analysis. RESULTS: In the univariate analysis, primary tumor size >5 cm was significantly associated with increased risk of distant metastasis (P=0.004; hazard ratio [HR] =3.05; 95% confidence interval [CI], 1.44–6.47). In the multivariate analysis, tumor size >5 cm remained predictive of distant metastasis (P<0.001; HR=5.49; 95% CI, 2.30–13.10). ABCC2 −24CC were shown to be associated with increased risk of distant metastasis (P=0.040; adjusted HR=2.34; 95% CI, 1.04–5.27). The combined genotype of ABCC2 −24CC − ABCB1 3435 CT+TT was associated with increased risk of distant and bone metastasis (P=0.020; adjusted HR=2.46; 95% CI, 1.15–5.26 and P=0.040; adjusted HR=3.70; 95% CI, 1.06–12.89, respectively). CONCLUSION: This study indicates that polymorphisms of ABCC2 and ABCB1 are independently associated with bone metastasis. Further prospective studies with larger sample sizes are needed to verify this finding.
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spelling pubmed-48351282016-04-22 ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen Sensorn, Insee Sukasem, Chonlaphat Sirachainan, Ekaphop Chamnanphon, Montri Pasomsub, Ekawat Trachu, Narumol Supavilai, Porntip Pinthong, Darawan Wongwaisayawan, Sansanee Onco Targets Ther Original Research BACKGROUND: Genetic polymorphisms of drug-metabolizing enzymes and transporters have been extensively studied with regard to tamoxifen treatment outcomes. However, the results are inconclusive. Analysis of organ-specific metastasis may reveal the association of these pharmacogenetic factors. The aim of this study is to investigate the impact of CYP3A5, CYP2D6, ABCB1, and ABCC2 polymorphisms on the risk of all distant and organ-specific metastases in Thai patients who received tamoxifen adjuvant therapy. METHODS: Genomic DNA was extracted from blood samples of 73 patients with breast cancer who received tamoxifen adjuvant therapy. CYP3A5 (6986A>G), CYP2D6 (100C>T), ABCB1 (3435C>T), and ABCC2 (−24C>T) were genotyped using allelic discrimination real-time polymerase chain reaction assays. The impacts of prognostic clinical factors and genetic variants on disease-free survival were analyzed using the Kaplan–Meier method and Cox regression analysis. RESULTS: In the univariate analysis, primary tumor size >5 cm was significantly associated with increased risk of distant metastasis (P=0.004; hazard ratio [HR] =3.05; 95% confidence interval [CI], 1.44–6.47). In the multivariate analysis, tumor size >5 cm remained predictive of distant metastasis (P<0.001; HR=5.49; 95% CI, 2.30–13.10). ABCC2 −24CC were shown to be associated with increased risk of distant metastasis (P=0.040; adjusted HR=2.34; 95% CI, 1.04–5.27). The combined genotype of ABCC2 −24CC − ABCB1 3435 CT+TT was associated with increased risk of distant and bone metastasis (P=0.020; adjusted HR=2.46; 95% CI, 1.15–5.26 and P=0.040; adjusted HR=3.70; 95% CI, 1.06–12.89, respectively). CONCLUSION: This study indicates that polymorphisms of ABCC2 and ABCB1 are independently associated with bone metastasis. Further prospective studies with larger sample sizes are needed to verify this finding. Dove Medical Press 2016-04-12 /pmc/articles/PMC4835128/ /pubmed/27110128 http://dx.doi.org/10.2147/OTT.S100905 Text en © 2016 Sensorn et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Sensorn, Insee
Sukasem, Chonlaphat
Sirachainan, Ekaphop
Chamnanphon, Montri
Pasomsub, Ekawat
Trachu, Narumol
Supavilai, Porntip
Pinthong, Darawan
Wongwaisayawan, Sansanee
ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen
title ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen
title_full ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen
title_fullStr ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen
title_full_unstemmed ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen
title_short ABCB1 and ABCC2 and the risk of distant metastasis in Thai breast cancer patients treated with tamoxifen
title_sort abcb1 and abcc2 and the risk of distant metastasis in thai breast cancer patients treated with tamoxifen
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835128/
https://www.ncbi.nlm.nih.gov/pubmed/27110128
http://dx.doi.org/10.2147/OTT.S100905
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