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TPMT and DPD polymorphisms: Efficient screening method for Indian patients considering taking Thiopurine and 5-FU

T F Ashavaid1, Rani Raghavan, Swarup Shah

  • 1P.D. Hinduja National Hospital & Medical Research Centre, Mumbai, India. dr_tashavaid@hindujahospital.com

Disease Markers
|December 29, 2009
PubMed
Abstract

Insights

Developing DNA tests for TPMT/DPD genetic variations in Indian patients is crucial for personalized cancer treatment. Identifying specific gene variants like G460A helps tailor drug choices, improving patient outcomes and safety.

Area of Science:

  • Pharmacogenomics
  • Molecular Diagnostics
  • Oncology

Background:

  • Genetic variations in TPMT and DPD genes influence drug metabolism and toxicity.
  • Lack of specific Indian population data for these pharmacogenetic markers hinders personalized cancer therapy.
  • DNA-based tests are essential for guiding treatment decisions in cancer patients.

Purpose of the Study:

  • To develop and validate molecular assays for identifying TPMT and DPD genetic polymorphisms in Indian patients.
  • To correlate identified genetic variations with patient responses and side effects to specific cancer drugs.

Main Methods:

  • Utilized molecular assays for screening TPMT alleles (*2, *3A, *3B, *3C) and DPD gene variations (IVS14+1(G-->A)).
  • Validated assay results using DNA sequencing.
  • Observed patient responses and side effects, including neutropenia and drug tolerance.

Main Results:

  • A patient with G460A homozygosity experienced neutropenia on 6-MP, leading to treatment cessation.
  • Two Acute Lymphoblastic Leukemia (ALL) patients with side effects showed wild-type alleles for common TPMT/DPD variations.
  • Two patients with wild-type alleles experienced 6-MP side effects initially but responded well later, suggesting multifactorial influences.

Conclusions:

  • G460A homozygosity identification enabled effective clinical management by stopping 6-MP.
  • Wild-type results in patients with side effects suggest the presence of rare or unidentified genetic variations.
  • Drug side effects can be influenced by multiple biological and environmental factors beyond common TPMT/DPD variants.

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