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Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms

Mladen V Tzvetkov1, Gerrit Behrens, Valerie P O'Brien

  • 1Department of Clinical Pharmacology, University Medical Center, Georg-August-University, Robert-Koch-Strasse 40, Göttingen, Germany. mtzvetk@gwdg.de

Pharmacogenomics
|September 10, 2011
PubMed
Abstract

Insights

Genetic variations in the ERCC1 gene may predict cisplatin-induced kidney damage in cancer patients. Specific ERCC1 polymorphisms were linked to reduced nephrotoxicity, offering potential biomarkers for personalized treatment.

Area of Science:

  • Pharmacogenomics
  • Nephrology
  • Oncology

Background:

  • Cisplatin is a widely used chemotherapy agent.
  • Nephrotoxicity is a significant dose-limiting side effect of cisplatin.
  • Interpatient variability in cisplatin-induced nephrotoxicity is not fully understood.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms and cisplatin-induced nephrotoxicity.
  • To identify potential genetic markers for predicting kidney damage.

Main Methods:

  • Analyzed polymorphisms in candidate genes (GSTM1, GSTT1, OCT1, OCT2, LARP2, ERCC1, XRCC1, EPO) in 79 cancer patients.
  • Assessed the relationship between genetic variations and changes in estimated glomerular filtration rate (eGFR).

Main Results:

  • Higher cisplatin dose correlated with decreased eGFR.
  • Two ERCC1 gene polymorphisms (8092C>A and Asn118Asn) were significantly associated with eGFR changes.
  • ERCC1 8092A allele and Asn118Asn C allele carriers showed no eGFR reduction compared to other carriers.

Conclusions:

  • Genetic polymorphisms in the ERCC1 gene may serve as valuable predictors of cisplatin-induced nephrotoxicity.
  • These findings could aid in personalizing cisplatin chemotherapy to minimize kidney damage.

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