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Disease Markers
Volume 27 (2009), Issue 5, Pages 231-238
http://dx.doi.org/10.3233/DMA-2009-0668

TPMT and DPD Polymorphisms: Efficient Screening Method for Indian Patients Considering Taking Thiopurine and 5-FU Drugs

T. F. Ashavaid, Rani Raghavan, Swarup Shah, Asha Kapadia, Sachin Almel, and Devendra Desai

Research Laboratories, P.D. Hinduja National Hospital & Medical Research Centre, Mumbai, India

Received 18 December 2009; Accepted 18 December 2009

Copyright © 2009 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction: Development of DNA-based tests for TPMT/DPD polymorphisms can help clinicians and patients to make important decisions about cancer treatment. Also, due to lack of Indian data, we aimed at the development and validation of these tests in Indian patients.

Materials and Methods: Molecular assays were used for identifying TPMT/DPD variations; validated by DNA sequencing.

Results: Molecular assays have been used for screening TPMT2, 3A, 3B, 3C alleles and IVS14+1(G→A) in DPD gene. A patient, exhibiting neutropenia on 6-MP was observed to be G460A-homozygote, while, two Acute Lymphoblastic Leukemia (ALL) patients with side-effects exhibited wild-type alleles. Two patients showing 6-MP side-effects and responding well to the same drug at later stage also carried wild-type alleles.

Discussion: G460A homozygosity in a patient allowed clinicians to stop 6-MP treatment, improving patient's health status. Two ALL patients showing side-effects were wild-type, indicating presence of unidentified rare variations. Two patients with wild-type allele showed side-effects during 6-MP treatment, but responded well to same drug at later stage, suggesting side-effects to be attributable to multiple biological and environmental processes. Absence of IVS14+1(G→A) in DPD gene will not exclude possibility of another mutation.

Conclusion: Molecular assays for determining common TPMT/DPD variations, can provide accurate diagnosis and efficient therapies in future clinical studies.