Pharmacogenomics of cisplatin-based chemotherapy in ovarian cancer patients of different ethnic origins

Aim: 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. Patients & 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 asso...