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The blood serum of tumor patients contains antibodies recognizing tumor-associated antigens and other molecular products of tumor growth. We studied the interaction of blood antibodies from breast cancer patients with synthetic peptides that were applied on the microchip surface. The serum from healthy volunteers and breast cancer patients was shown to contain antibodies that interact with various peptides. Statistically significant between-group differences were observed in the level of binding with 122 informative peptides (0.01% of the total number of peptides on a microchip). Analysis of antibodies that interact with the peptide panel holds much promise for the diagnostics of breast cancer.

Genetic variation in DNA repair genes can alter an individual's capacity to repair damaged DNA and influence the risk of cancer. We tested seven polymorphisms in DNA repair genes XRCC1, ERCC2, XRCC3, XRCC2, EXOI and TP53 for a possible association with breast cancer risk in a sample of 672 case and 672 control Russian women. An association was observed for allele A of the polymorphism XRCC1 (R399Q) rs25487 (co-dominant model AA vs. GG: OR 1.76, P = 0.003; additive model OR 1.28, P = 0.005; dominant model: OR 1.29, P = 0.03; recessive model OR 1.63, P = 0.008). Allele T of the polymorphism ERCC2 (D312N) rs1799793 was also associated with breast cancer risk (co-dominant model TT vs. CC: OR 1.43, P = 0.04; additive model OR 1.21, P = 0.02; dominant model: OR 1.30, P = 0.02), but the association became insignificant after applying Bonferroni correction. No association with breast cancer was found for the remaining SNPs. In summary, our study provides evidence that polymorphisms in DNA repair genes may play a role in susceptibility to breast cancer in the population of ethnical Russians.

Telomere length and telomerase activity have been hypothesized to play a role in cancer development. The aim of our study was to investigate the association of allelic variants of three functional polymorphisms rs2853669, rs2736100, and rs7726159 in the telomerase reverse transcriptase (TERT) gene with the risk of the breast cancer and prostate cancer in Russian population. Six hundred sixty women with breast cancer, 372 men with prostate cancer, and corresponding control groups of 523 women and 363 men were included in the present case-control study. We observed an association of allele rs2853669 C with increased risk of prostate cancer (co-dominant model TC vs. TT OR = 1.65, P = 0.002; additive model OR = 1.42, P = 0.005; dominant model: OR = 1.64, P = 0.001) and allele rs7726159 A with reduced risk of this malignancy (сo-dominant model: AA vs. CC OR = 0.42, P = 0.002; additive model: OR = 0.69, P = 0.002; dominant model: OR = 0.67, P = 0.01; recessive model: OR = 0.48, P = 0.005). None of the studied polymorphisms showed an association with the risk of breast cancer. Our results provide evidence that the TERT gene variability modulate prostate cancer predisposition in ethnical Russians.

The aim of this study was to implement massive parallel sequencing (MPS) technology in clinical genetics testing. We developed and tested an amplicon-based method for resequencing the BRCA1 and BRCA2 genes on an Illumina MiSeq to identify disease-causing mutations in patients with hereditary breast or ovarian cancer (HBOC). The coding regions of BRCA1 and BRCA2 were resequenced in 96 HBOC patient DNA samples obtained from different sample types: peripheral blood leukocytes, whole blood drops dried on paper, and buccal wash epithelia. A total of 16 random DNA samples were characterized using standard Sanger sequencing and applied to optimize the variant calling process and evaluate the accuracy of the MPS-method. The best bioinformatics workflow included the filtration of variants using GATK with the following cut-offs: variant frequency >14%, coverage (>25x) and presence in both the forward and reverse reads. The MPS method had 100% sensitivity and 94.4% specificity. Similar accuracy levels were achieved for DNA obtained from the different sample types. The workflow presented herein requires low amounts of DNA samples (170 ng) and is cost-effective due to the elimination of DNA and PCR product normalization steps.

In the present study we investigated the association of a number of polymorphic changes in antioxidant system genes (SNPs rs1050450 in the GPX1 gene, rs1695 and rs1138272 in the GSTP1 gene and rs4880 in the MnSOD gene) with the risk of prostate cancer. The association of disease stage and PSA levels with specific genotypes was also analyzed. A study was conducted with the participation of 736 Russian men. We compared the frequency of occurrence of the studied alleles in patients with prostate cancer (392) to a control group (344) of men without a history of cancer. Genotyping was performed by real-time PCR. Comparison of frequencies of alleles and genotypes were performed using logistic regression analysis. No statistically significant association with the risk of prostate cancer was found for any of the SNPs studied (p > 0.05). For SNP rs1695 in the GSTP1 gene, a correlation with cancer disease stage was observed: a GG genotype is significantly more common in patients with PCa in the 3rd and 4th stage than 1st and 2nd (OR[95%CI] = 2.66[1.15-6.18], p = 0.02). Both studied SNPs of GSTP1 gene are associated with the level of PSA: the GG rs1695 and the TT rs1138272 genotypes are associated with higher PSA levels (p = 1.5*10(-3)).

The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can input into predisposition to breast cancer. The purpose of actual study was to analyze the associations of polymorphic loci CYP17/B1rs10556836, CYP1A 1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of development of breast cancer in Russian residents of the Western-Siberian region of Russia. The rates of alleles and genotypes of the given loci were determined in sampling of women suffering with breast cancer (n = 670 females) and in control group (480 females without oncological diseases). The sub-groups of patients with breast cancer in pre-menopause--and post-menopause were analyzed separately. The border-line association of locus CYP17A1rs743572 is demonstrated with increasing of risk of breast cancer during pre-menopause (allele C: p = 0.04). Among the rest of polymorphic loci no association was detected.

Introduction: Multiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (CaP). However, the risk conferred in men living in Russia is unknown., Materials and Methods: In this work we studied the association of rs6983267, rs10090154, and rs1447295 single nucleotide polymorphisms (SNPs) with a risk of CaP development in men of Caucasoid descent living in the Siberian region of Russia. Three 8q24 SNPs were genotyped by real-time polymerase chain reaction in histologically confirmed CaP "cases" (n = 392) and clinically evaluated "controls" (n = 344). To evaluate the SNP effects on CaP susceptibility, odds ratio (OR) and confidence interval (CI) 95% were calculated. Allele and genotype frequencies in the groups were compared using logistic regression; differences were considered statistically significant if P<0.05., Results: We showed statistically significant association of the A allele of rs1447295 (OR [CI 95%] = 1.96 [1.37-2.81], P<0.0001) and the T allele of rs10090154 (OR [CI 95%] = 2.14 [1.41-3.26], P<0.0001) with CaP. The T-A rs10090154 to rs1447295 haplotype was also associated with CaP (OR [CI 95%] = 2.47 [1.59-3.85], P<0.0001). There was no significant association with the T allele of rs6983267: OR [CI 95%] = 0.9 [0.73-1.11], P> 0.05., Conclusion: Thus, our investigation confirms the role of chromosomal region 8q24 in the development of CaP in the Russian population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.

Allelic variants of folate cycle enzyme genes can contribute to predisposition to cancer. The impact of polymorphic loci A2756G of MTR gene and of C1420T of SHMT1 gene for the risk of prostatic cancer was studied in residents of West Siberia. The frequency of alleles of these loci in patients (N=371) and controls (N=285) was determined and the data were statistically processed. No statistically significant association with prostatic cancer was detected for any of the studied loci.

A retrospective multicenter trial with participation of 7 large clinics of Moscow and Moscow Region has been performed to characterize complications after correction of genital prolapse with application of the PROLIFT system. The trial enrolled women with uterine and vaginal prolapse of stage II-IV by POP-Q classification. The women also had anatomic and functional defects of the adjacent organs. From January 2005 to March 2008 all the patients have undergone vaginal extraperitoneal colpopexy using Prolift system. The results of the trial showed that extraperitoneal colpopexy with application of the Prolift system should not be considered as a low-invasive intervention and therefore it is not valid to use this technique as a routine method of genital prolapse treatment as in 29.5% cases the operation is accompanied with complications of different severity.

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

Breast cancer is the most incident cancer among women. We investigated the role of polymorphisms of folate metabolizing genes MTHFR (C677T and A1298C), SHMT1 (C1420T) and MTHFD (G1258A) in genetic susceptibility to this type of cancer. We determined allele and genotype frequencies in case (850 women with sporadic form of breast cancer) and control (810 women) groups. None of these polymorphisms was significantly associated with breast cancer risk. To increase statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. Meta-analysis also revealed no significant association of studied SNPs with breast cancer.

Polymorphisms within intron 2 of the FGFR2 gene have been associated with increased risk of breast cancer (BC) in European and Asian populations. The study by Easton et al reported two FGFR2 SNPs, rs2981582 and rs7895676, to be among those most strongly associated with BC risk. Statistical modeling suggested that rs7895676 was the variant responsible for the association observed in the region. In this work, we studied the association between seven FGFR2 SNPs, including rs2981582 and rs7895676, and BC risk in the Russian population of 766 case and 665 control women from Siberia, Russian Federation. In our population, allelic frequencies and the magnitude of linkage disequilibrium (LD) were different from those observed in European and Asian populations. The following three SNPs were significantly associated with BC in our study: rs7895676[C] (odds ratio (OR)=1.28 (1.12-1.43), P=1.7 x 10(-3)), rs2981582[T] (OR=1.46 (1.30-1.62), P=2 x 10(-6)) and rs3135718[G] (OR=1.43 (1.27-1.58), P=6 x 10(-6)). The latter two SNPs were in strong (r(2)=0.95) LD in our sample. Maximum likelihood analysis showed that the model, including rs7895676, only explains that the association is significantly (P<0.001) worse than any of the models, including either rs2981582 or rs3135718. Thus, in addition to the confirmation of association of FGFR2 with the BC risk in this new population, our study has suggested that rs7895676 is not likely to represent the causative variant.

The incidence of homozygote deletion of glutathione S-transferase genes M1 and T1 (null genotypes; or GSTM1"-" and GSTT1"-") was studied in breast cancer patients living in Altai Krai. DNA was isolated from blood samples of 695 breast cancer patients (291 patients with familial cancer and 404 patients with sporadic cancer) and 263 women without history of tumor diseases. The frequency of GSTM1"-" and GSTT1"-" genotypes was estimated in breast cancer patients (47.2 and 19.1%, respectively) and non-cancer participants (46.8 and 19.0%, respectively). No differences were found in the frequency of genotypes. The frequency of genotype combination GSTM1"-"+GSTT1"-" in patients with sporadic breast cancer (11.6%, 47 of 404 patients) was higher than in the control (6.1%, 16 of 263 patients; OR=2.03; 95% CI=2.09-3.83; p=0.02). The genotype frequency of genes in the control group did not differ from that in European residents of the Caucasian race.

he incidence of MnSOD genotypes in residents of the Altai Region suffering from breast cancer and individuals without a history of cancer corresponded to the Hardy-Weinberg equilibrium. No association of MnSOD with the incidence of sporadic breast cancer was detected. No association of MnSOD, tobacco smoking, or menopausal status, on the one hand, and breast cancer development, on the other, was detected.

The authors have modified a method for determining circulating immune complexes in the complement fixation test. It is shown that with the 7% concentration of polyethylene glycol (PEG)-6000, there is a more complete precipitation of low- and medium-molecular weight immune complexes. The time and temperature of serum incubation were optimized when PEG-6000 was obtained. The use of the soluble circulating immune complexes (sCIC) prepared from human serum as a standard for the construction of a standard plot could substantially enhance the sensitivity of the method (0.325 microg/ ml). The content of circulating immune complexes was studied in donors and in patients with connective tissue dysplasia (CTD) by the improved procedure. In the group of donors, the mean level of sCIC was 0.62 +/- 0.24 mg/ml. In the CTD group, that was 2.32 +/- 0.93 mg/ml; the serum concentrations of sCIC ranging from 1.1 to 5.0 mg/ml. In the donors and patients, the detection rate of serum sCIC was 100%. The proposed method may be clinically used to measure the human serum levels of sCIC.

Urinary incontinence (UI) in patients with genital prolapse is not always related to stress. It may result from dyslocation of the vesicourethral segment. While genital prolapse in young patients after a single normal delivery is common manifestation of connective tissue dysplasia (CTD) at the level of the reproductive system, 51.8% cases of UI may be of neurogenic origin and present as dysfunction of the vesicourethral segment and pelvic diaphragm. Unstability of the bladder and urethra in these cases may represent CTD at the level of the pelvic organs.