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Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients

Rebecca Suk1, Sarada Gurubhagavatula, Sohee Park

  • 1Massachusetts General Hospital and Harvard School of Public Health, Boston, MA 02115, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 5, 2005
PubMed
Abstract

Insights

A specific ERCC1 gene variant (C8092A) increases the risk of severe gastrointestinal toxicity in non-small cell lung cancer patients receiving platinum chemotherapy.

Area of Science:

  • Genetics
  • Oncology
  • Pharmacogenomics

Background:

  • The ERCC1 gene plays a crucial role in DNA repair via the nucleotide excision repair pathway.
  • Polymorphisms in ERCC1, including C8092A and codon 118, may influence DNA repair capacity and treatment toxicity.
  • Understanding these genetic variations is important for predicting patient outcomes in cancer therapy.

Purpose of the Study:

  • To investigate the association between ERCC1 C8092A and codon 118 polymorphisms and severe toxicity in non-small cell lung cancer (NSCLC) patients.
  • To determine if these polymorphisms predict treatment-related adverse events in patients undergoing first-line platinum-based chemotherapy.

Main Methods:

  • Logistic regression models were employed to analyze data from 214 stage III and IV NSCLC patients.
  • The study assessed the association between ERCC1 C8092A and codon 118 polymorphisms and grade 3 or 4 toxicity.
  • Performance status and treatment regimen were included as adjusting covariates.

Main Results:

  • No significant association was found between either polymorphism and overall or hematologic grade 3 or 4 toxicity.
  • However, the ERCC1 C8092A variant allele was significantly linked to an increased risk of grade 3 or 4 gastrointestinal toxicity (OR, 2.33; P = 0.03).

Conclusions:

  • Carrying at least one ERCC1 8092A allele is associated with a greater than twofold increased risk of severe gastrointestinal toxicity.
  • This finding is relevant for platinum-treated NSCLC patients, even after adjusting for performance status and treatment regimen.

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