Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh

Introduction: Pharmacogenomic studies contribute to genetic information in preventing severe side effects of drugs. Genetic polymorphisms in drug metabolizing enzymes such as dihydropyrimidine dehydrogenase (DPD) had been associated with variable clinical outcomes in many commonly prescribed chemoth...

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Main Authors: Teh, Lay Kek, Salleh, Mohd Zaki
Format: Research Reports
Language:English
Published: Research Management Institute (RMI) 2010
Subjects:
Online Access:https://ir.uitm.edu.my/id/eprint/27162/
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author Teh, Lay Kek
Salleh, Mohd Zaki
author_facet Teh, Lay Kek
Salleh, Mohd Zaki
author_sort Teh, Lay Kek
building UiTM Institutional Repository
collection Online Access
description Introduction: Pharmacogenomic studies contribute to genetic information in preventing severe side effects of drugs. Genetic polymorphisms in drug metabolizing enzymes such as dihydropyrimidine dehydrogenase (DPD) had been associated with variable clinical outcomes in many commonly prescribed chemotherapy drugs including 5-Fluorouracil and irinotecan. Objectives: The review of literature had shed lights to the importance and possible impact of genetic polymorphism of DPYD and TPMT in individualization of drug therapy for 5-FU and thiopurines. However, there were no data reported for Malaysian. Current study thus aimed to explore the role of pharmacogenetics in personalized medicine in our own population. Materials and methods: Genotyping methods for DPYD and TPMT were developed using dHPLC and allele specific PCR respectively. 5-FU levels were measured in colorectal cancer patients using developed method. DNA from healthy volunteers and patients were screened. Results: Genotyping of DPYD had detected one reported mutation DPYD*5, two new mutations in exon 14 1823 T>C and 1827 G>A and one intronic reagion of exon 13, 13 IVS-11G>A with allele frequencies of 14.5%, .9.1%, 9.1% and 0.9% respectively. Genotyping for TPMT revealed 7 (7%) to be heterozygous for TPMT variant alleles. The predominant allele detected is TPMT*3C and is in concordance with previous studies done on Southeast Asian populations.
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spelling uitm-271622020-01-10T05:25:22Z https://ir.uitm.edu.my/id/eprint/27162/ Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh Teh, Lay Kek Salleh, Mohd Zaki Cancer Introduction: Pharmacogenomic studies contribute to genetic information in preventing severe side effects of drugs. Genetic polymorphisms in drug metabolizing enzymes such as dihydropyrimidine dehydrogenase (DPD) had been associated with variable clinical outcomes in many commonly prescribed chemotherapy drugs including 5-Fluorouracil and irinotecan. Objectives: The review of literature had shed lights to the importance and possible impact of genetic polymorphism of DPYD and TPMT in individualization of drug therapy for 5-FU and thiopurines. However, there were no data reported for Malaysian. Current study thus aimed to explore the role of pharmacogenetics in personalized medicine in our own population. Materials and methods: Genotyping methods for DPYD and TPMT were developed using dHPLC and allele specific PCR respectively. 5-FU levels were measured in colorectal cancer patients using developed method. DNA from healthy volunteers and patients were screened. Results: Genotyping of DPYD had detected one reported mutation DPYD*5, two new mutations in exon 14 1823 T>C and 1827 G>A and one intronic reagion of exon 13, 13 IVS-11G>A with allele frequencies of 14.5%, .9.1%, 9.1% and 0.9% respectively. Genotyping for TPMT revealed 7 (7%) to be heterozygous for TPMT variant alleles. The predominant allele detected is TPMT*3C and is in concordance with previous studies done on Southeast Asian populations. Research Management Institute (RMI) 2010-12 Research Reports NonPeerReviewed text en https://ir.uitm.edu.my/id/eprint/27162/1/LP_TEH%20LAY%20KEK%20RMI%2010_5.pdf Teh, Lay Kek and Salleh, Mohd Zaki (2010) Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh. (2010) [Research Reports] (Unpublished)
spellingShingle Cancer
Teh, Lay Kek
Salleh, Mohd Zaki
Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh
title Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh
title_full Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh
title_fullStr Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh
title_full_unstemmed Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh
title_short Cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-Fluorouracil / Teh Lay Kek And Mohd Zaki Salleh
title_sort cancerpharmacogenomics: the relevance of genetic profile in optimization drug therapy for azathiopurine and 5-fluorouracil / teh lay kek and mohd zaki salleh
topic Cancer
url https://ir.uitm.edu.my/id/eprint/27162/