Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment

Wanaporn Charoenchokthavee,1 Duangchit Panomvana,1 Virote Sriuranpong,2 Nutthada Areepium1 1Department of Pharmacy Practice, Faculty of Pharmaceutical Science, 2Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Tamoxifen (TAM)...

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Autores principales:	Charoenchokthavee W, Panomvana D, Sriuranpong V, Areepium N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	CYP2D6 CYP3A5 tamoxifen breast cancer prevalence Thai Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/dd4638e7387d4ee68431b6537441d76d
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spelling	oai:doaj.org-article:dd4638e7387d4ee68431b6537441d76d2021-12-02T08:16:15ZPrevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment1179-1314https://doaj.org/article/dd4638e7387d4ee68431b6537441d76d2016-08-01T00:00:00Zhttps://www.dovepress.com/prevalence-of-cyp2d62-cyp2d64-cyp2d610-and-cyp3a53-in-thai-breast-canc-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Wanaporn Charoenchokthavee,1 Duangchit Panomvana,1 Virote Sriuranpong,2 Nutthada Areepium1 1Department of Pharmacy Practice, Faculty of Pharmaceutical Science, 2Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Tamoxifen (TAM) is used in breast cancer treatment, but interindividual variabilities in TAM-metabolizing enzymes exist and have been linked to single nucleotide polymorphisms in the respective encoding genes. The different alleles and genotypes of these genes have been presented for Caucasians and Asians. This study aimed to explore the prevalence of the incomplete functional alleles and genotypes of the CYP2D6 and CYP3A5 genes in Thai breast cancer patients undergoing TAM treatment.Patients and methods: In total, 134 Thai breast cancer patients were randomly invited to join the Thai Tamoxifen Project. Their blood samples were collected and extracted for individual DNA. The alleles and genotypes were determined by real-time polymerase chain reaction with TaqMan® Drug Metabolism Genotyping Assays.Results: The patients were aged from 27.0 years to 82.0 years with a body mass index range from 15.4 to 40.0, with the majority (103/134) in the early stage (stages 0–II) of breast cancer. The median duration of TAM administration was 17.2 months (interquartile range 16.1 months). Most (53%) of the patients were premenopausal with an estrogen receptor (ER) and progesterone receptor (PR) status of ER+/PR+ (71.7%), ER+/PR- (26.9%), ER-/PR+ (0.7%), and ER-/PR- (0.7%). The allele frequencies of CYP2D61, CYP2D62, CYP2D64, CYP2D610, CYP3A51, and CYP3A53 were 72.9%, 3.2%, 1.1%, 22.8%, 37.3%, and 62.7%, respectively, while the genotype frequencies of CYP2D61/1, CYP2D61/2, CYP2D62/2, CYP2D64/4, CYP2D61/10, CYP2D62/10, CYP2D64/10, CYP2D610/10, CYP3A51/1, CYP3A51/3, and CYP3A53/3 were 9.7%, 2.2%, 3.7%, 1.5%, 15.7%, 9.7%, 3.7%, 53.7%, 13.4%, 47.8%, and 38.8%, respectively.Conclusion: The majority (97.8%) of Thai breast cancer patients undergoing TAM treatment carry at least one incomplete functional allele, including 20.9% of the patients who carry only incomplete functional alleles for both the CYP2D6 and CYP3A5 genes. This research indicates the high prevalence of these defective alleles that are involved in TAM-metabolic pathways that might further affect TAM treatment. Keywords: CYP450, SNPs, antihormone, oncology, pharmacogenetics, pharmacogenomicsCharoenchokthavee WPanomvana DSriuranpong VAreepium NDove Medical PressarticleCYP2D6CYP3A5tamoxifenbreast cancerprevalenceThaiNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2016, Iss Issue 1, Pp 149-155 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	CYP2D6 CYP3A5 tamoxifen breast cancer prevalence Thai Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	CYP2D6 CYP3A5 tamoxifen breast cancer prevalence Thai Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Charoenchokthavee W Panomvana D Sriuranpong V Areepium N Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment
description	Wanaporn Charoenchokthavee,1 Duangchit Panomvana,1 Virote Sriuranpong,2 Nutthada Areepium1 1Department of Pharmacy Practice, Faculty of Pharmaceutical Science, 2Medical Oncology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: Tamoxifen (TAM) is used in breast cancer treatment, but interindividual variabilities in TAM-metabolizing enzymes exist and have been linked to single nucleotide polymorphisms in the respective encoding genes. The different alleles and genotypes of these genes have been presented for Caucasians and Asians. This study aimed to explore the prevalence of the incomplete functional alleles and genotypes of the CYP2D6 and CYP3A5 genes in Thai breast cancer patients undergoing TAM treatment.Patients and methods: In total, 134 Thai breast cancer patients were randomly invited to join the Thai Tamoxifen Project. Their blood samples were collected and extracted for individual DNA. The alleles and genotypes were determined by real-time polymerase chain reaction with TaqMan® Drug Metabolism Genotyping Assays.Results: The patients were aged from 27.0 years to 82.0 years with a body mass index range from 15.4 to 40.0, with the majority (103/134) in the early stage (stages 0–II) of breast cancer. The median duration of TAM administration was 17.2 months (interquartile range 16.1 months). Most (53%) of the patients were premenopausal with an estrogen receptor (ER) and progesterone receptor (PR) status of ER+/PR+ (71.7%), ER+/PR- (26.9%), ER-/PR+ (0.7%), and ER-/PR- (0.7%). The allele frequencies of CYP2D61, CYP2D62, CYP2D64, CYP2D610, CYP3A51, and CYP3A53 were 72.9%, 3.2%, 1.1%, 22.8%, 37.3%, and 62.7%, respectively, while the genotype frequencies of CYP2D61/1, CYP2D61/2, CYP2D62/2, CYP2D64/4, CYP2D61/10, CYP2D62/10, CYP2D64/10, CYP2D610/10, CYP3A51/1, CYP3A51/3, and CYP3A53/3 were 9.7%, 2.2%, 3.7%, 1.5%, 15.7%, 9.7%, 3.7%, 53.7%, 13.4%, 47.8%, and 38.8%, respectively.Conclusion: The majority (97.8%) of Thai breast cancer patients undergoing TAM treatment carry at least one incomplete functional allele, including 20.9% of the patients who carry only incomplete functional alleles for both the CYP2D6 and CYP3A5 genes. This research indicates the high prevalence of these defective alleles that are involved in TAM-metabolic pathways that might further affect TAM treatment. Keywords: CYP450, SNPs, antihormone, oncology, pharmacogenetics, pharmacogenomics
format	article
author	Charoenchokthavee W Panomvana D Sriuranpong V Areepium N
author_facet	Charoenchokthavee W Panomvana D Sriuranpong V Areepium N
author_sort	Charoenchokthavee W
title	Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment
title_short	Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment
title_full	Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment
title_fullStr	Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment
title_full_unstemmed	Prevalence of CYP2D62, CYP2D64, CYP2D610, and CYP3A53 in Thai breast cancer patients undergoing tamoxifen treatment
title_sort	prevalence of cyp2d62, cyp2d64, cyp2d610, and cyp3a53 in thai breast cancer patients undergoing tamoxifen treatment
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/dd4638e7387d4ee68431b6537441d76d
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Prevalence of CYP2D6*2, CYP2D6*4, CYP2D6*10, and CYP3A5*3 in Thai breast cancer patients undergoing tamoxifen treatment

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