Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan

Janelle M. Hoskins, Gary L. Rosner, Mark J. Ratain, Howard L. McLeod, Federico Innocenti

Research output: Contribution to journalArticle

Abstract

Aims: A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m 2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan. Materials & methods: DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Associations between genotypes and haplotypes and log(absolute neutrophil count nadirs) were assessed by linear regression. Results: No associations were observed. Conclusion: Our findings suggest that the genes we tested do not influence toxicity of irinotecan when adminstered at 300-350 mg/m2.

Original languageEnglish (US)
Pages (from-to)1139-1146
Number of pages8
JournalPharmacogenomics
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2009

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Keywords

  • Irinotecan
  • PARP1
  • Pharmacogenetics
  • TDP1
  • TOP1
  • XRCC1

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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