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Thymidylate synthase gene polymorphisms effecting 5-FU response in breast cancer patients

Kalyana Kumar1, Mohana Vamsy, Kaiser Jamil

  • 1Research Department, Indo American Cancer Institute and Research Center, Banjara Hills, Road No 14, Hyderabad, Andhra Pradesh, India.

Cancer Biomarkers : Section a of Disease Markers
|June 24, 2010
PubMed

Insights

Genetic variations in thymidylate synthase (TYMS) influence 5-Fluorouracil response in breast cancer patients. TYMS polymorphisms may help personalize chemotherapy, reducing adverse drug reactions and improving treatment outcomes.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Adverse drug reactions (ADRs) can stem from genetic variations in drug-metabolizing genes.
  • Thymidylate synthase (TYMS) is a key enzyme in folate metabolism and the target of 5-Fluorouracil chemotherapy.
  • Single nucleotide polymorphisms (SNPs) in TYMS may affect drug response and breast cancer (BC) risk.

Purpose of the Study:

  • To investigate the frequencies of TYMS polymorphisms in breast cancer patients.
  • To correlate TYMS genetic variations with patient response to 5-Fluorouracil therapy.
  • To assess the role of TYMS polymorphisms in breast cancer risk and drug response.

Main Methods:

  • Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) were used to analyze TYMS polymorphisms.
  • Genotyping was performed on 140 breast cancer patients and 150 control individuals.
  • Allele and genotype frequencies were compared between groups, and correlation with drug response was analyzed.

Main Results:

  • The TYMS1494del polymorphism showed a statistically significant difference in allele frequencies between BC patients (0.85 deletion, 0.15 insertion) and controls (0.95 deletion, 0.04 insertion).
  • Combined genotypes indicated a 2-fold increased risk of BC.
  • Poor drug response was observed in BC patients with 2R/3R and 2R/2R TYMS genotypes, suggesting a link between these polymorphisms and treatment efficacy.

Conclusions:

  • TYMS polymorphisms, particularly the 1494del variant, are significantly associated with breast cancer risk.
  • Specific TYMS genotypes correlate with poor response to 5-Fluorouracil, highlighting their potential role in predicting treatment outcomes.
  • Genetic screening of TYMS polymorphisms can aid in individualizing 5-Fluorouracil therapy for breast cancer patients.

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