Pharmacogenetic markers of toxicity for chemotherapy in colorectal cancer patients

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Lucía Cortejoso1, Luis A López-Fernández

  • 1Laboratory of Pharmacogenetics & Pharmacogenomics, Pharmacy Department, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid, Spain.

Pharmacogenomics
|August 23, 2012
PubMed

Insights

Predicting colorectal cancer treatment toxicity is possible through genetic variations. Analyzing polymorphisms in key genes can help tailor chemotherapy for better efficacy and fewer adverse reactions.

Area of Science:

  • Oncology
  • Pharmacogenomics

Background:

  • Colorectal cancer chemotherapy often causes severe adverse reactions, impacting treatment effectiveness.
  • Genetic variations are linked to toxicity from common colorectal cancer drugs like fluoropyrimidines, oxaliplatin, irinotecan, and cetuximab.
  • Comparing studies is challenging due to complex treatments and varied toxicity classifications.

Purpose of the Study:

  • To analyze the association between genetic polymorphisms and chemotherapy-induced toxicity in colorectal cancer patients.
  • To review the current understanding and future directions in pharmacogenomic prediction of colorectal cancer treatment toxicity.

Main Methods:

  • Systematic review and analysis of genetic polymorphisms in key genes.
  • Focus on polymorphisms in DPYD, TYMS, MTHFR, ABCB1, UGT1A1, ERCC1, ERCC2, XRCC1, GSTT1, and GSTM1.
  • Evaluation of associations with toxicity from fluoropyrimidines, oxaliplatin, irinotecan, and cetuximab.

Main Results:

  • Specific genetic variations (polymorphisms) in genes like DPYD and UGT1A1 are associated with increased risk of severe adverse reactions.
  • Polymorphisms in genes involved in drug metabolism and DNA repair pathways influence patient response and toxicity.
  • The identified genetic markers show potential for predicting individual patient susceptibility to chemotherapy toxicity.

Conclusions:

  • Genetic profiling can aid in predicting and managing chemotherapy-induced toxicity in colorectal cancer.
  • Tailoring treatment based on genetic variations can improve therapeutic outcomes and patient safety.
  • Further research is needed to standardize toxicity classifications and integrate pharmacogenomics into clinical practice for colorectal cancer treatment.

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