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Updated: Jul 3, 2026
06:21
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
[Genetic polymorphisms related to fluoropyrimidine sensitivity and toxicity]
1Division of Gastric Surgery, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan.
Gan to Kagaku Ryoho. Cancer & Chemotherapy
|July 18, 2008
Summary
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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