Pharmacogenomics of Cisplatin-Based Chemotherapy in Ovarian Cancer Patients of Different Ethnic Origins

Abstract

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 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. Conclusion: 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.

Original submitted: 9 June 2011; Revision submitted: 22 September 2011

KEYWORDS::

• chemotherapy
• cisplatin
• DNA polymorphism
• ethnic diversity
• ovarian cancer

Financial & competing interests disclosure

This study was supported by Federal Program “Scientific and Pedagogical Cadre for Innovative Russia” for 2009–2013 years (contract No. P1204), programs of the Russian Academy of Sciences “Molecular and Cell Biology” and “Fundamental Science for Medicine”, Program of Support for Leading Scientific Schools of the Ministry of Science and Technology of the Russian Federation and Russian Foundation for Basic Research (grant No. 11-04-00913). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by Federal Program “Scientific and Pedagogical Cadre for Innovative Russia” for 2009–2013 years (contract No. P1204), programs of the Russian Academy of Sciences “Molecular and Cell Biology” and “Fundamental Science for Medicine”, Program of Support for Leading Scientific Schools of the Ministry of Science and Technology of the Russian Federation and Russian Foundation for Basic Research (grant No. 11-04-00913). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.