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Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
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Cisplatin pharmacogenetics, DNA repair polymorphisms, and esophageal cancer outcomes

Penelope A Bradbury1, Matthew H Kulke, Rebecca S Heist

  • 1Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada.

Pharmacogenetics and Genomics
|July 22, 2009
PubMed
Abstract

Insights

Genetic variations in DNA repair pathways influence esophageal cancer patient outcomes. Specific nucleotide excision repair (NER) gene polymorphisms predict improved survival with cisplatin chemotherapy, highlighting potential personalized treatment strategies.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Genetic variations in nucleotide excision repair (NER) influence DNA repair capacity.
  • Reduced NER capacity may increase susceptibility to DNA-damaging chemotherapy like cisplatin.
  • Investigating NER polymorphisms could identify predictive biomarkers for esophageal cancer treatment.

Purpose of the Study:

  • To investigate the predictive significance of functional NER single nucleotide polymorphisms (SNPs) in esophageal cancer patients.
  • To assess the interaction between NER polymorphisms and cisplatin treatment on patient survival.
  • To evaluate overall survival (OS) and progression-free survival (PFS) as endpoints.

Main Methods:

  • Genotyping of four NER polymorphisms: XPD Asp312Asn, XPD Lys751Gln, ERCC1 8092C/A, and ERCC1 codon 118C/T.
  • Analysis of polymorphism-cisplatin treatment interactions for OS and PFS.
  • Haplotype analyses were performed to confirm findings.

Main Results:

  • No significant associations were found for ERCC1 118 polymorphism.
  • Significant interactions between cisplatin treatment and polymorphisms in XPD 312, XPD 751, and ERCC1 8092 were observed for both OS and PFS.
  • In cisplatin-treated patients, variant alleles of XPD 312, XPD 751, and ERCC1 8092 were associated with improved OS and PFS.
  • In patients not receiving cisplatin, variant alleles of XPD 751 and ERCC1 8092 were associated with worse survival.

Conclusions:

  • Nucleotide excision repair (NER) gene polymorphisms are associated with overall survival (OS) and progression-free survival (PFS) in esophageal cancer.
  • These polymorphisms may serve as predictive biomarkers for benefit from cisplatin therapy.
  • Further validation is needed to confirm their role in personalized esophageal cancer treatment.

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