Metabolomics and pharmacogenetics based 5-fluorouracil monitoring in colorectal cancer patients

Zakaria, Bannur and Mohd Zaki, Salleh and Hashim, Hazwanie and Tom, Hennessy and Md Nor, Azmi and MH, Zailani and Prabu, Ramasamy and ZA, Zakaria and Suneet, S and Ngow, Harris Abdullah and Henry, Guy M. and Teh, Laykek (2014) Metabolomics and pharmacogenetics based 5-fluorouracil monitoring in colorectal cancer patients. International Journal of Pharmacy and Pharmaceutical Sciences, 6 (Supp 2). pp. 288-295. ISSN 0975-1491

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Abstract

Objective: To provide quick and accurate clinical diagnostic tools those are currently not available leading to improper management of colorectal cancer (CRC) patients. Methods: The metabolomic profiles of 10 CRC patients treated with 5-fluorouracil and 24 healthy volunteers were analysed. The subjects were genotyped for UGT1A1*28, DPYD 1896 T>C and DPYD*5. Results: Our results show alterations in the metabolism of bile acid, glycolysis and fatty acid in patients. The distinctive metabolite profiles established using PLSDA identify several biomarkers for diagnostic use in clinical settings. The predictive PLSDA model revealed 100% accuracy of metabolites differentiating CRC patients and healthy volunteers. In addition, the metabolic profiles associated with different genotypes of DPYD and UGT1A1 explains the impact of genetic variation on differential drug responses. Conclusion: Pharmacogenetics and metabolomics profiles are potential platforms for more comprehensive monitoring of patient's disease progress and drug response. Further study is however needed to validate the use of biomarkers identified. Keywords: Metabolomics, Pharmacogenetics, Polymorphism, Colorectal cancer (CRC), 5-fluorouracil (5-FU)

Item Type:	Article (Journal)
Additional Information:	3011/42698
Uncontrolled Keywords:	Metabolomics, Pharmacogenetics, Polymorphism, Colorectal cancer (CRC), 5-fluorouracil (5-FU)
Subjects:	R Medicine > RC Internal medicine
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Internal Medicine
Depositing User:	Mrs Noor Azlin Asnam
Date Deposited:	28 Apr 2015 09:20
Last Modified:	21 Sep 2017 13:12
URI:	http://irep.iium.edu.my/id/eprint/42698

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