Ethnic Differences in Susceptibility to the Effects of Platinum- Based Chemotherapy

Abstract

There is substantial interindividual variability in the efficacy and tolerability of antican - cer drugs. Such differences can be greater between individuals of different ethnicities. The clinical studies demonstrate that individuals from Asia (East Asia) are more sus - ceptible to the effects of platinum-containing chemotherapies than their Western coun -terparts. To determine whether population-related genomics (i.e., frequencies of DNA polymorphisms) contribute to differences in patient outcomes, polymorphisms in 109 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle, and apopto - sis were tested in Russian (Caucasians) and Yakut (North Asians) ovarian cancer patients receiving cisplatin-based chemotherapy. Totally, 232 polymorphisms were genotyped in individual DNA samples using conventional PCR and arrayed primer extension technol -ogy. Single nucleotide polymorphisms (SNPs) in more than 30 genes were found to be associated with one or more of clinical end points (i.e., tumor response, progression-free survival, overall survival, and side effects). However, all associations between SNPs and clinical outcomes were specific for each of ethnic group studied. These findings let us to propose the existence of distinctive ethnic-related characteristics in molecular mecha - nisms determining the sensitivity of patients to platinum drug effects.