Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen

Breast cancer is a group of multigenic diseases. It is the most common cancer diagnosed among women worldwide and is often treated with tamoxifen. Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could...

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Autores:
Ariza Márquez, Yeimy Viviana
Briceño, Ignacio
Aristizábal, Fabio
Niño, Luis Fernando
Yosa Reyes, Juvenal
Tipo de recurso:
Fecha de publicación:
2019
Institución:
Universidad Simón Bolívar
Repositorio:
Repositorio Digital USB
Idioma:
eng
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oai:bonga.unisimon.edu.co:20.500.12442/2676
Acceso en línea:
http://hdl.handle.net/20.500.12442/2676
Palabra clave:
Breast cancer
Cancer - Treatment
Cancer - Genetic aspects
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Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
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network_name_str Repositorio Digital USB
repository_id_str
dc.title.eng.fl_str_mv Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
title Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
spellingShingle Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
Breast cancer
Cancer - Treatment
Cancer - Genetic aspects
title_short Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
title_full Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
title_fullStr Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
title_full_unstemmed Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
title_sort Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
dc.creator.fl_str_mv Ariza Márquez, Yeimy Viviana
Briceño, Ignacio
Aristizábal, Fabio
Niño, Luis Fernando
Yosa Reyes, Juvenal
dc.contributor.author.none.fl_str_mv Ariza Márquez, Yeimy Viviana
Briceño, Ignacio
Aristizábal, Fabio
Niño, Luis Fernando
Yosa Reyes, Juvenal
dc.subject.eng.fl_str_mv Breast cancer
Cancer - Treatment
Cancer - Genetic aspects
topic Breast cancer
Cancer - Treatment
Cancer - Genetic aspects
description Breast cancer is a group of multigenic diseases. It is the most common cancer diagnosed among women worldwide and is often treated with tamoxifen. Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could alter enzyme activity. We evaluated SNPs in patients from Colombia in South America who were receiving tamoxifen treatment for breast cancer. Allelic diversity in the CYP2D6 gene was found in the studied population, with two patients displaying the poor-metaboliser phenotype. Molecular dynamics and trajectory analyses were performed for CYP2D6 from these two patients, comparing it with the common allelic form (CYP2D6*1). Although we found no significant structural change in the protein, its dynamics differ significantly from those of CYP2D6*1, the effect of such differential dynamics resulting in an inefficient enzyme with serious implications for tamoxifen-treated patients, increasing the risk of disease relapse and ineffective treatment.
publishDate 2019
dc.date.accessioned.none.fl_str_mv 2019-02-21T20:07:27Z
dc.date.available.none.fl_str_mv 2019-02-21T20:07:27Z
dc.date.issued.none.fl_str_mv 2019-02-21
dc.type.eng.fl_str_mv article
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.identifier.issn.none.fl_str_mv 20452322
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12442/2676
identifier_str_mv 20452322
url http://hdl.handle.net/20.500.12442/2676
dc.language.iso.eng.fl_str_mv eng
language eng
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dc.rights.license.spa.fl_str_mv Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
rights_invalid_str_mv Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional
http://purl.org/coar/access_right/c_abf2
dc.publisher.eng.fl_str_mv Springer
dc.source.eng.fl_str_mv Scientific Reports
dc.source.spa.fl_str_mv Vol. 9, No. 2521 (2019)
institution Universidad Simón Bolívar
dc.source.uri.eng.fl_str_mv https://www.nature.com/articles/s41598-018-38340-6
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spelling Licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacionalhttp://purl.org/coar/access_right/c_abf2Ariza Márquez, Yeimy Vivianaa715988f-d240-4ddb-9823-fd2c0913bb62Briceño, Ignacio0adcd0b1-abc1-4b3a-b5fc-98a88896d5daAristizábal, Fabio9c24243f-8e11-4399-9761-f9b17414d3adNiño, Luis Fernandofaa0c1c4-4ca2-4a75-a505-a25d72dcd7afYosa Reyes, Juvenal83d2abea-d832-4a13-8dd3-e553c61757a82019-02-21T20:07:27Z2019-02-21T20:07:27Z2019-02-2120452322http://hdl.handle.net/20.500.12442/2676Breast cancer is a group of multigenic diseases. It is the most common cancer diagnosed among women worldwide and is often treated with tamoxifen. Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could alter enzyme activity. We evaluated SNPs in patients from Colombia in South America who were receiving tamoxifen treatment for breast cancer. Allelic diversity in the CYP2D6 gene was found in the studied population, with two patients displaying the poor-metaboliser phenotype. Molecular dynamics and trajectory analyses were performed for CYP2D6 from these two patients, comparing it with the common allelic form (CYP2D6*1). Although we found no significant structural change in the protein, its dynamics differ significantly from those of CYP2D6*1, the effect of such differential dynamics resulting in an inefficient enzyme with serious implications for tamoxifen-treated patients, increasing the risk of disease relapse and ineffective treatment.engSpringerScientific ReportsVol. 9, No. 2521 (2019)https://www.nature.com/articles/s41598-018-38340-6Breast cancerCancer - TreatmentCancer - Genetic aspectsDynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifenarticlehttp://purl.org/coar/resource_type/c_6501Ferlay, J. et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in globocan 2012. Int. J. Cancer 136, E359–E386, https://doi.org/10.1002/ijc.29210 (2015).Zafra-Ceres, M. et al. Influence of CYP2D6 polymorphisms on serum levels of tamoxifen metabolites in Spanish women with breast cancer. Int. J. Med. Sci., https://doi.org/10.7150/ijms.5708 (2013).Hoskins, J. M., Carey, L. A. & McLeod, H. L. CYP2D6 and tamoxifen: DNA matters in breast cancer, https://doi.org/10.1038/nrc2683 (2009).The Cancer Atlas estimated new breast cancer cases and deaths by region, http://canceratlas.cancer.org/the-burden/breast-cancer. Accessed: 2018-03-15 (2012).Knaul, F. M. et al. Meeting the emerging challenge of breast and cervical cancer in low- and middle-income countries. Int J Gynaecol Obstet, https://doi.org/10.1016/j.ijgo.2012.03.024 (2012).Luciani, S., Cabanes, A., Prieto-Lara, E. & Gawryszewski, V. 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