title: Pharmacogenomics of cisplatin-based chemotherapy in ovarian cancer patients of different ethnic origins.
abstract: OBJECTIVE
  There is a substantial difference between Asians and Caucasians in their reaction to platinum drugs. To determine whether population-related genomics contribute to differences in patient outcomes, pharmacogenomic relevance of polymorphisms in some genes, the protein activities of which may affect aspects of cisplatin metabolism, were evaluated.
  
  
  METHODS
  Nineteen polymorphisms in ten genes were tested for correlations with the efficacy and toxicity of a cisplatin-cyclophosphamide regimen in Yakut and Russian patients with ovarian cancer.
  
  
  RESULTS
  The CYP2E1 7632T>A polymorphism was associated with progression-free survival (p = 0.015) in Yakuts. In Russians, progression-free survival was correlated with the GSTP1 Ile105Val polymorphism (p = 0.004). Yakut patients with the GSTT1-null genotype had a higher risk for nephrotoxicity. By contrast, in the Russian group, nephrotoxicity was more frequent among patients with heterozygous ERCC1 genotypes. Severe emesis in Yakuts was independently associated with two polymorphisms in the CYP2E1 gene but in Russians, it was more common in patients with the GSTT1-null genotype. Differences in genotypic correlations with anemia were also observed.
  
  
  CONCLUSIONS
  Significant differences in genotype distribution between Russian and Yakut women were observed for ten of the 19 polymorphisms, but none of them seemed to be a clear casual candidate and further studies involving more markers are required.
authors.affiliation: Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia. khrunin@img.ras.ru
authors.forename: Andrey
authors.initials: A
authors.lastname: Khrunin
authors.forename: Feodosia
authors.initials: F
authors.lastname: Ivanova
authors.forename: Alexey
authors.initials: A
authors.lastname: Moisseev
authors.forename: Denis
authors.initials: D
authors.lastname: Khokhrin
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Sleptsova
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.forename: Svetlana
authors.initials: S
authors.lastname: Limborska
mesh_terms: D044466:Asian People / Q000235:genetics*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D012426:Russia; D044465:White People / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D019392:Cytochrome P-450 CYP2E1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin