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[Genetic polymorphisms related to fluoropyrimidine sensitivity and toxicity]

Masanori Terashima1

  • 1Division of Gastric Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan.

Gan to Kagaku Ryoho. Cancer & Chemotherapy
|July 18, 2008
PubMed

Insights

Genetic variations in key enzymes affect how patients respond to 5-fluorouracil (5-FU) chemotherapy, influencing both its effectiveness and potential toxicity. Understanding these genetic polymorphisms can personalize cancer treatment strategies.

Area of Science:

  • Pharmacogenomics
  • Cancer Therapeutics
  • Molecular Biology

Context:

  • Fluoropyrimidines, like 5-fluorouracil (5-FU), are widely used anticancer drugs.
  • Their efficacy and toxicity are influenced by genetic variations in metabolic enzymes.
  • Understanding these variations is crucial for optimizing patient outcomes.

Purpose:

  • To review the impact of genetic polymorphisms on the sensitivity and toxicity of fluoropyrimidine-based chemotherapy.
  • To highlight specific genetic markers associated with 5-FU efficacy and adverse events.
  • To emphasize the need for clinical trials to validate genetic predictors.

Summary:

  • Genetic polymorphisms in thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and methylenetetrahydrofolate reductase (MTHFR) significantly affect 5-FU activity.
  • Variations such as tandem repeat numbers in the TS enhancer, 3'-UTR deletions, DPD mutations (e.g., IVS14+1G>A), and MTHFR C677T influence patient response and toxicity.
  • These genetic factors can predict higher sensitivity, increased antitumor activity, or severe toxicity.

Impact:

  • Personalized chemotherapy regimens based on individual genetic profiles can be developed.
  • Improved prediction of 5-FU efficacy and toxicity will enhance treatment safety and effectiveness.
  • Clinical trials are needed to prospectively validate these genetic markers for routine use in cancer treatment planning.

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