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DNA polymorphism is an important factor in the interindividual variations in the reactions of patients to the same drugs. In the current study, the polymorphism in the OCT2, GGT1, HO1, and DNASE1 genes were evaluated for the correlation with cisplatin nephrotoxicity in ovarian cancer patients. An increased risk of nephrotoxicity (OR = 2.19, 95% CI 0.953–5.038 p = 0.088) was noted for patients with the homozygous GGT1 T/T genotype (rs5751901). An analysis of associations between polymorphisms of the studied genes and other side effects of the used chemotherapy regimens revealed the pronounced correlation between thrombocytopenia and DNASE1 G/A polymorphism (rs1053874) (χ2 = 6.49; p = 0.039).

Distribution of several widespread, extensively studied polymorphic variants of genes of the cytosol glutathione-S-transferase subfamily (GSTA1, GSTM1, GSTM3, GSTP1, and GSTT1) has been studied in samples from Russian populations of European Russia, as well as Komi and Yakut populations used for comparison. Analysis of the GSTP1 and GSTM3 polymorphisms has not revealed significant differences in the distribution of alleles of the loci, including two-site GSTP1 haplotypes, in most Russian populations and between Komi populations. Only in the Yakut sample have a significant difference been found with respect to these loci in each pairwise comparison. Regarding the GSTT1 and GSTA1 genes, in addition to differences between the Yakut population and all other populations with respect to the GSTA1 gene, it has been found that the frequencies of the GSTT1 0/0 deletion genotype and GSTA1 −69T allele in the Russian sample from Mezen’ (Arkhangel’sk oblast) are substantially lower than in other Russian populations and Komi populations. The significance of these differences has been confirmed by tests for heterogeneity of the entire pool of Russian populations.

Siberia and Northwestern Russia are home to over 40 culturally and linguistically diverse indigenous ethnic groups, yet genetic variation and histories of peoples from this region are largely uncharacterized. We present deep whole-genome sequencing data (∼38×) from 28 individuals belonging to 14 distinct indigenous populations from that region. We combined these data sets with additional 32 modern-day and 46 ancient human genomes to reconstruct genetic histories of several indigenous Northern Eurasian populations. We found that Siberian and East Asian populations shared 38% of their ancestry with a 45,000-yr-old Ust’-Ishim individual who was previously believed to have no modern-day descendants. Western Siberians trace 57% of their ancestry to ancient North Eurasians, represented by the 24,000-yr-old Siberian Mal'ta boy MA-1. Eastern Siberian populations formed a distinct sublineage that separated from other East Asian populations ∼10,000 yr ago. In addition, we uncovered admixtures between Siberians and Eastern European hunter-gatherers from Samara, Karelia, Hungary, and Sweden (from 8000–6600 yr ago); Yamnaya people (5300–4700 yr ago); and modern-day Northeastern Europeans. Our results provide new insights into genetic histories of Siberian and Northeastern European populations and evidence of ancient gene flow from Siberia into Europe.

Polymorphism ofglutathione-S-transferase (GSTA1, GSTM1, GSTM3, GSTP1, and GSTT1) and DNA repair (ERCC1, ERCC2, and XRCC1) genes in samples of ovarian cancer patients and healthy women of the Russian ethnic group was studied. A trend in the allele frequency variation of ERCC2 gene single nucleotide polymorphism (rs13181, A > C) was revealed. The A allele frequency was higher in the sample of patients (60,6% versus 52,9%, P = 0.058).

Aim: Cisplatin and its analogs are potent antitumor agents. However, their use is restricted by significant variability in tumor response and toxicity. There is a great need to identify genetic markers to predict the most important adverse events and patient outcomes. Materials & methods: We have evaluated the association between polymorphisms in 106 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle and apoptosis, and outcomes in 104 ovarian cancer patients receiving cisplatin–cyclophosphamide chemotherapy. Arrayed primer extension technology was used to genotype 228 SNPs. Results: Ten SNPs in nine genes were found to be associated with one or more of the assessed clinical end points. SNPs in TPMT and NQO1 were significantly associated with progression-free survival. Polymorphisms in ERCC5, RAD52, MUTYH and LIG3 correlated with the occurrence of severe neutropenia. SNPs in NAT2 and EPHX1 were associated with anemia and nephrotoxicity, respectively. A SNP in ADH1C was correlated with complete tumor response. Conclusion: The results obtained suggest that SNPs in different genes involved in drug metabolism can be important in identifying patients at risk for nonresponse to or toxicity from cisplatin-based treatment. Original submitted 2 August 2013; Revision submitted 25 November 2013

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

Several studies examined the fine-scale structure of human genetic variation in Europe. However, the European sets analyzed represent mainly northern, western, central, and southern Europe. Here, we report an analysis of approximately 166,000 single nucleotide polymorphisms in populations from eastern (northeastern) Europe: four Russian populations from European Russia, and three populations from the northernmost Finno-Ugric ethnicities (Veps and two contrast groups of Komi people). These were compared with several reference European samples, including Finns, Estonians, Latvians, Poles, Czechs, Germans, and Italians. The results obtained demonstrated genetic heterogeneity of populations living in the region studied. Russians from the central part of European Russia (Tver, Murom, and Kursk) exhibited similarities with populations from central-eastern Europe, and were distant from Russian sample from the northern Russia (Mezen district, Archangelsk region). Komi samples, especially Izhemski Komi, were significantly different from all other populations studied. These can be considered as a second pole of genetic diversity in northern Europe (in addition to the pole, occupied by Finns), as they had a distinct ancestry component. Russians from Mezen and the Finnic-speaking Veps were positioned between the two poles, but differed from each other in the proportions of Komi and Finnic ancestries. In general, our data provides a more complete genetic map of Europe accounting for the diversity in its most eastern (northeastern) populations.