Sergei Feshchenko

Republican Science-Practical Center Cardiology, Myenyesk, Minsk, Belarus

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Publications (4)34.9 Total impact

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    ABSTRACT: Mutations in the NBS1 gene have been identified as disease-causing mutations in patients with Nijmegen Breakage Syndrome (NBS), but their clinical impact on breast cancer susceptibility has remained uncertain. We determined the frequency of 2 NBS mutations, 657del5 and R215W, in two large series of breast cancer cases and controls from Northern Germany and from the Republic of Belarus. The 5-bp-deletion 657del5 was identified in 15/1,588 cases (0.9%) from Belarus and in 1/1,076 cases (0.1%) from Germany but in only 1/1,014 population controls from Belarus and 0/1017 German controls (p < 0.01). The missense substitution R215W was observed in 9/1,588 Byelorussian and 9/1,076 German patients (0.6% and 0.8%, respectively) but was also present in 5/1,014 Byelorussian and 2/1,017 German control individuals (adjusted OR = 1.9, 95%CI 0.8-4.6, p = 0.18). Studies of lymphoblastoid cell lines revealed that NBS1/p95 protein levels were reduced to 70% in cells from a heterozygous breast cancer patient carrying R215W and to 15% in cells from a NBS patient compound heterozygous for 657del5/R215W suggesting that the R215W substitution may be associated with protein instability. Levels of radiation-induced phosphorylation of Nbs1/p95(Ser343) were reduced to 60% and 35% of wildtype, respectively. Neither age at diagnosis nor family history of breast cancer differed significantly between carriers and noncarriers of NBS mutations. The combined data are in line with an about 3-fold increase in breast cancer risk for female NBS heterozygotes (OR 3.1; 95%CI 1.4-6.6) and indicate that the 657del5 deletion and perhaps the R215W substitution contribute to inherited breast cancer susceptibility in Central and Eastern Europe.
    International Journal of Cancer 02/2008; 122(4):802-6. · 6.20 Impact Factor
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    ABSTRACT: The NBS1/p95 protein has a pivotal role in the sensing and repair of chromosome breaks. A missense mutation in the NBS1 gene, I171V, has recently been associated with a ninefold increased risk of breast cancer in Polish patients. Positive associations have also been reported for leukaemia and larynx cancer suggesting that I171V could be a more general susceptibility factor for malignancies. We investigated the prevalence of this mutation in two large hospital-based case-control series from Germany and from the Republic of Belarus. The I171V substitution was detected in 20/1,636 Byelorussian breast cancer patients and in 18/1,014 Byelorussian controls (OR: 0.68; 95%CI: 0.36-1.30, P=0.3). The I171V substitution was furthermore detected in 10/1,048 German breast cancer patients and in 7/1,017 German controls (OR: 1.39; 95%CI: 0.53-3.67, P=0.7). There were no significant differences between I171V carriers and non-carriers among the cases with regard to age at diagnosis, family history or bilateral occurrence of disease. A meta-analysis of all hitherto available studies did not reveal a difference in the prevalence of I171V between breast cancer cases and controls (OR: 1.05; 95%CI: 0.64-1.74, P=0.9). We conclude that the I171V substitution is unlikely to constitute a strong risk factor for breast cancer in our study populations.
    Breast Cancer Research and Treatment 12/2007; 112(1):75-9. · 4.47 Impact Factor
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    Journal of Clinical Oncology 08/2007; 25(19):e26. · 18.04 Impact Factor
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    ABSTRACT: The 1100delC mutation of the cell cycle checkpoint kinase 2 (CHEK2) gene confers an increased risk for breast cancer, but the clinical impact of other CHEK2 gene variants remains unclear. We determined the frequency of two functionally relevant CHEK2 gene mutations, I157T and IVS2+1G > A, in two large series of breast cancer cases and controls from two independent populations. Our first series consisted of a hospital-based cohort of 996 German breast cancer cases and 486 population controls, and the second series consisted of 424 breast cancer patients and 307 population controls from the Republic of Belarus. The missense substitution I157T was identified in 22/996 cases (2.2%) vs. 3/486 controls (0.6%; OR = 3.6, 95% CI 1.1-12.2, p = 0.044) in the German population and in 24/424 cases (5.7%) vs. 4/307 controls (1.3%; OR = 4.5, 95% CI 1.6-13.2, p = 0.005) in the Byelorussian cohorts. The splicing mutation IVS2+1G > A was infrequent in both populations, being observed in 3/996 German and 4/424 Byelorussian patients (0.3% and 0.9%, respectively) and in 1/486 German controls (0.2%; adjusted OR = 4.0, 95% CI 0.5-30.8, p = 0.273). Heterozygous CHEK2 mutation carriers tended to be diagnosed at an earlier age in both populations, but these differences did not reach statistical significance. Family history of breast cancer did not differ between carriers and noncarriers. Our data indicate that the I157T allele, and possibly the IVS2+1G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility.
    International Journal of Cancer 08/2005; 116(2):263-6. · 6.20 Impact Factor