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Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients

Mutlu Dogan1, Halil G Karabulut, Ajlan Tukun

  • 1Dept of Medical Oncology, School of Medicine, Ankara University, Ankara, Turkey. mutludogan1@yahoo.com

Asian Pacific Journal of Cancer Prevention : APJCP
|July 18, 2012
PubMed
Abstract

Insights

Pharmacogenetic variations in genes like DPYD and MTHFR may increase the risk of severe toxicity from chemotherapy drugs such as fluorouracil (5FU), capecitabine, and methotrexate.

Area of Science:

  • Oncology
  • Pharmacogenetics
  • Cancer Therapeutics

Background:

  • Antimetabolites are crucial cancer drugs but can cause severe toxicity, including fatal outcomes.
  • Identifying genetic factors influencing toxicity is essential for patient safety.

Purpose of the Study:

  • To investigate the association between pharmacogenetic polymorphisms and severe toxicity in cancer patients receiving fluorouracil (5FU), capecitabine, or methotrexate.
  • To evaluate genetic variations in MTHFR, TS, DPYD, XPD, and XRCC1 genes in relation to clinical toxicity and alanine transaminase (ALT) elevation.

Main Methods:

  • A cohort of 18 cancer patients experiencing severe antimetabolite toxicity was analyzed.
  • Genotyping was performed for MTHFR C667T, TS VNTR, DPYD IVS14+1G/A, XPD Lys751Gln, and XRCC1 Arg399Gln polymorphisms.

Main Results:

  • Patients presented with various malignancies including osteosarcoma, gastrointestinal cancers, and breast cancer.
  • Common toxicities included mucositis and dermatitis; ALT elevation was noted in the methotrexate group, with two toxic deaths observed.
  • Rare allele frequencies for DPYD, TS, MTHFR, XPD, and XRCC1 polymorphisms were higher than in the general population.

Conclusions:

  • Pharmacogenetic profiling may help predict and mitigate antimetabolite-induced toxicity.
  • These findings suggest a role for pharmacogenetics in personalizing cancer therapy to improve patient outcomes and safety.

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