Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident

The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornob...

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Datum:2016
Hauptverfasser: Shkarupa, V.M., Mishcheniuk, O.Y., Henyk-Berezovska, S.O., Palamarchuk, V.O., Klymenko, S.V.
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Veröffentlicht: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2016
Schriftenreihe:Experimental Oncology
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Zitieren:Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident / V.M. Shkarupa, O.Y. Mishcheniuk, S.O. Henyk-Berezovska, V.O. Palamarchuk, S.V. Klymenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 257-260. — Бібліогр.: 20 назв. — англ.

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spelling irk-123456789-1376912018-06-18T03:05:34Z Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident Shkarupa, V.M. Mishcheniuk, O.Y. Henyk-Berezovska, S.O. Palamarchuk, V.O. Klymenko, S.V. Original contributions The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornobyl accident. Materials and Methods: XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. Results: In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04–12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. Conclusions: The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”. 2016 Article Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident / V.M. Shkarupa, O.Y. Mishcheniuk, S.O. Henyk-Berezovska, V.O. Palamarchuk, S.V. Klymenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 257-260. — Бібліогр.: 20 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137691 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Shkarupa, V.M.
Mishcheniuk, O.Y.
Henyk-Berezovska, S.O.
Palamarchuk, V.O.
Klymenko, S.V.
Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
Experimental Oncology
description The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornobyl accident. Materials and Methods: XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. Results: In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04–12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. Conclusions: The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”.
format Article
author Shkarupa, V.M.
Mishcheniuk, O.Y.
Henyk-Berezovska, S.O.
Palamarchuk, V.O.
Klymenko, S.V.
author_facet Shkarupa, V.M.
Mishcheniuk, O.Y.
Henyk-Berezovska, S.O.
Palamarchuk, V.O.
Klymenko, S.V.
author_sort Shkarupa, V.M.
title Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
title_short Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
title_full Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
title_fullStr Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
title_full_unstemmed Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
title_sort polymorphism of dna repair gene xpd lys751gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2016
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/137691
citation_txt Polymorphism of dna repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the chornobyl accident / V.M. Shkarupa, O.Y. Mishcheniuk, S.O. Henyk-Berezovska, V.O. Palamarchuk, S.V. Klymenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 257-260. — Бібліогр.: 20 назв. — англ.
series Experimental Oncology
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fulltext Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ��� POLYMORPHISM OF DNA REPAIR GENE XPD Lys751Gln AND CHROMOSOME ABERRATIONS IN LYMPHOCYTES OF THYROID CANCER PATIENTS EXPOSED TO IONIZING RADIATION DUE TO THE CHORNOBYL ACCIDENT V.M. Shkarupa1, *, O.Y. Mishcheniuk1, S.O. Henyk-Berezovska2, V.O. Palamarchuk3, S.V. Klymenko1 1State Institution «National Research Centre for Radiation Medicine of National Academy of Medical Sciences of Ukraine», Kyiv 04050, Ukraine 2State Institution «Institute of Hereditary Pathology of National Academy of Medical Sciences of Ukraine, Lviv 79000, Ukraine 3Ukrainian Scientific and Practical Center of Endocrine Surgery, Transplantation of Endocrine Organs and Tissues of the Ministry of Health of Ukraine, Kyiv 01021, Ukraine The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornobyl accident. Materials and Methods: XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. Results: In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04–12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. Conclusions: The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”. Key Words: XPD gene polymorphisms, thyroid cancer, Chornobyl disaster, chromosome aberrations. The diversity of XP� protein role in transcription processes and �NA repair status underlines the value of a polymorphic gene status in a suscepti�ility to cancer pathology [���]. However� the role of XP� polymorphisms in the pathogenesis of malignant tumors remains controversial. One and the same al- leles of polymorphic gene XPD may have the favora�le or protective effect in terms of oncogenesis� depend- ing on the ethnicity of the population� the type of tis- sue� from which the tumor develops� and the impact of environmental factors [��9]. For these reasons� the literature data on the role of polymorphisms of gene XPD in cancer risk and tumor progression� especially under the impact of ionizing radiation �IR�� are am�igu- ous and further research is required. XP� is an important component of nucleotide exci- sion repair �NER� and is a�le to resist radiation-induced �NA damage [��]. �NA repair gene polymorphisms result in significant differences in the efficiency of re- pair of already existing �NA damage. The changes of functional activity of specific proteins that function in the reparative systems� potentially lead to mutagen- esis. However� the role of individual polymorphic �NA repair system markers in chromosome mutagenesis can not �e definitively esta�lished. Search for impor- tant genetic markers of individual genotoxic sensitivity to radiation effects among highly polymorphic genes today also gave not definitive results [�����]. Among the possi�le reasons for this� it was indicated the use of different approaches for the assessment of the mu- tagenesis �the measure different metrics: a�errations of chromosomes� micronuclei� �NA strand �reaks� in populations� that have the different distri�ution of genotypes of the polymorphic markers [��]. How- ever� the study of the relationship of polymorphisms of genes with the level of chromosomal damages in the cohorts of persons exposed to IR� may increase the sensitivity of cytogenetic �iomarkers as the indicators of the genotoxic effects� as well as may help in the identification of the risk groups. IR is a causative factor of the radiogenic thyroid cancer �TC�. According to a result of large-scale radia- tion and epidemiological studies� the frequency of the TC among of various contingents of the population exposed to radiation as a result of the Chorno�yl ac- cident is increasing. In several studies was found the relationship �etween of high level of the chromosomal a�errations in the culture of peripheral �lood lym- Submitted: August 01, 2016. *Correspondence: E-mail: Shkarupa_vlad@bigmir.net Abbreviations used: IR — ionizing radiation; IRS — individual radio- sensitivity; NER — nucleotide excision repair; NPP — nuclear po- wer plant; PCR — polymerase chain reaction; TC — thyroid cancer. Exp Oncol ���� ��� 4� ������� ��� Experimental Oncology ��� �������� ���� ��ecem�er� phocytes of persons exposed to IR and the risk of the developing of the TC [�9]. The aim of this work was to analyze the relation- ship �etween polymorphisms of �NA repair gene XPD Lys���Gln and frequency and spectrum of chromo- some a�errations in the culture of peripheral �lood lymphocytes of TC patients exposed to IR due to the Chorno�yl accident. MATERIALS AND METHODS Genotyping of polymorphisms XPD Lys���Gln was performed �y polymerase chain reaction �PCR� with electrophoretic visualization of PCR products in �% agarose gel in ��� TC patients. �� TC patients exposed to IR due to Chorno�yl accident created the group I. Among them� there were �� cleanup workers at the Chorno�yl nuclear power plant �participants in liquidation of the Chorno�yl nuclear power plant �NPP� accident consequences� group IA�; and �� evacuees and residents from areas contaminated with radionuclides �group IB�. To the group II we in- cluded �4 TC patients without history of IR exposure. The control group was selected from Ukrainian population and accounted 4� persons without cancer. Analysis of the association �etween the XPD Lys- ���Gln polymorphism and frequency and spectrum of chromosome a�errations �metaphase analysis of chromosomal a�errations in peripheral �lood lym- phocyte cultures� was performed in �� TC patients� who had not received chemotherapy or radiotherapy. On average� ��� metaphases were analyzed ����� ���� of the first mitosis per person. �ifferential count- ing of chromosome- and chromatid-type a�errations was conducted. The patients were treated in National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine. The study has �een performed in accordance with ethics rules for �iomedical research. All patients gave an informed consent for the participation in the study. Compliance with Hardy — Wein�erg equili�rium was assessed using Fisher’s exact test. Odds ratio �OR� was assessed using logistic regression analysis for the three models of inheritance: multiplicative� additive� and dominant. For frequency and spectrum of chromosomal a�errations mean values and their standard error �M ± m� were calculated. Estimation of group frequencies of chromosomal a�errations was calculated �y avera ging individual frequencies for individuals with certain genotype. Intergroup dif- ferences of cytogenetic parameters were evaluated using Fisher’s exact test. RESULTS AND DISCUSSION Previously� we have investigated features of the relationship �etween the XPD Lys���G polymorphism and the risks of TC development in persons exposed to IR after Chorno�yl disaster [��]. In comparison with the previous work� in this study we increased the num�er of patients in the control group� these results are shown in Ta�le � and Ta�le �. In the total group of TC patients� regardless of his- tory of radiation exposure� the distri�ution of geno- types corresponded to Hardy — Wein�erg equation. Conversely� among TC patients without influence of IR in history �group II�� the distri�ution of genotypes did not meet Hardy — Wein�erg equation �Ta�le ��. Table 1. Distribution of individual gene polymorphisms Lys751Gln XPD, the frequency of the variant allele of the gene XPD, and the genotypes dis- tribution matching Hardy — Weinberg equation Groups XPD genotype, n (%) Hardy — Weinberg χ2, р Lys751Lys Lys751Gln Gln751Gln V allele (751Gln) frequency TC (all pa- tients), n = 102 31 (30.39) 55 (53.92) 16 (15.69) 0.43 1.07 р = 0.30 I, n = 38 11 (28.95) 17 (44.74) 10 (26.31) 0.49 0.42 р = 0.52 IA, n = 10 1 (10.00) 3 (30.00) 6 (60.00) 0.75 0.40 р = 0.53 IB, n = 28 10 (35.71) 14 (50.00) 4 (14.29) 0.39 0.06 р = 0.80 II, n = 64 20 (31.24) 38 (59.38) 6 (9.38) 0.39 3.91 р = 0.05 Control, n = 45 20 (44.44) 21 (46.67) 4 (8.89) 0.32 0.21 р = 0.65 Table 2. Association of XPD gene Lys751Gln polymorphism with risk of TC Groups Multiplicative model Additive model Dominant model OR; 95% confidence interval (CI); p value TC (all pa- tients; n = 102) vs control group (n = 45) Allele Lys751 0.64 (0.38–1.08) Allele Gln751 1.56 (0.93–2.64) р = 0.09 Lys751/Lys751 0.68 (0.26–1.13) Lys751/Gln751 1.34 (0.66–2.70) Gln751/Gln751 1.91 (0.60–6.07) р = 0.08 Lys751/Lys751 + Lys751/Gln751 0.52 (0.16–1.67) Gln751/Gln751 1.91 (0.60–6.07] р = 0.27 I (n = 38) vs control group (n = 45) Allele Lys751 0.50 (0.27–0.94) Allele Gln751 2.00 (1.06–3.75) р = 0.03 Lys751/Lys751 0.51 (0.20–1.27) Lys751/Gln751 0.93 (0.39–2.20) Gln751/Gln751 3.66 (1.04–12.84) р = 0.03 Lys751/Lys751 + Lys751/Gln751 0.27 (0.08–0.96) Gln751/Gln751 3.66 (1.04–12.84) р = 0.03 II (n = 64) vs control group (n = 45) Allele Lys751 0.74 (0.42–1.31) Allele Gln751 1.35 (0.76–2.38) р = 0.30 Lys751/Lys751 0.57 (0.26–1.25) Lys751/Gln751 1.67 (0.77–3.61) Gln751/Gln751 1.06 (0.28–4.00) р = 0.26 Lys751/Lys751 + Lys751/Gln751 0.94 (0.25–3.55) Gln751/Gln751 1.06 (0.28–4.00) р = 0.93 Analysis of the literature and comparison of the results showed that the frequency of the variant allele XPD ���Gln in the group IB and group II did not dif- fer �y this parameter in persons without cancer from Poland — �.�9� �.�9 and �.��� respectively [9]. �if- �.�9� �.�9 and �.��� respectively [9]. �if-�.�9� �.�9 and �.��� respectively [9]. �if-.�9� �.�9 and �.��� respectively [9]. �if-�9� �.�9 and �.��� respectively [9]. �if-� �.�9 and �.��� respectively [9]. �if- and �.��� respectively [9]. �if-.��� respectively [9]. �if-��� respectively [9]. �if-. �if- �if- ferences in frequency of polymorphic allele of gene XPD ���Gln in com�ined group of persons �group I� exposed to IR as a result of the Chorno�yl accident are statistically not significant compared to the group II. The frequency of variant alleles of the gene XPD ���Gln in persons of this group was increased compared with group II ��.49 and �.�9� respectively�� �ut the difference was not significant �p = �.���. The frequency of homozygous allele carriers Gln���Gln �among all other genotypes� in TC patients exposed to IR was significantly higher than in TC pa- tients without IR exposure in history �Ta�le �� — ��.��% and 9.��%� respectively� χ� = �.��� p = �.���. The fre- Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ��9 quency of this genotype in a group of other categories of Chorno�yl victims �evacuees and residents of con- taminated territories� did not differ significantly �χ� = �.��� p = �.�4�. The OR was calculated in different models of inheri- tance �Ta�le ��. When compared with a control group of Ukrainian population in homozygous carriers of the minor allele of the gene XPD Lys���Gln� exposed to IR� it was found a significantly increased risk of TC: OR = �.��; p = �.�� �9�% CI �.�4���.�4�. When compared with a control group of Ukrainian population in patients without a history of exposure to IR� carrier state of ho- mozygous minor alleles of the gene XPD Lys���Gln was not associated with risk of TC: OR = �.��; p = �.9� �9�% CI �.���4.���. In our research the IR was a factor that determined the high risk of TC depending on Lys���Gln XPD polymorphism. Association analysis was performed �etween frequency of spontaneous chromosome a�errations in TC patients and XPD Lys���Gln polymorphism. The significant link of XPD Lys���Gln gene polymorphism with elevated chromosome a�errations was o�served only in the group IB of TC patients evacuated and residents of contaminated areas in Ukraine. The aver- age frequency of chromosome a�errations in patients with genotype Gln���Gln was significantly higher than in heterozygotes Lys���Gln ��.�� ± �.�9 and �.�� ± �.�� a�errations/per ��� cells� respectively� p = �.����. Although a similar trend was o�served in relation to Lys���Lys homozygotes� the difference in this case has insufficient level of certainty due to two times less sampling. �ifferences in frequency of chro- mosome- and chromatid-type a�errations depending on the genotype in this group were not found. In participants of liquidation of the Chorno�yl NPP accident consequences of group IA� in which the cyto- genetic analysis was held� there were none individuals homozygous �y the major allele XPD Lys���Lys. The tendency to increase the frequency of a�errations in individuals with genotype Gln���Gln compared with heterozygotes XPD Lys���Gln was insufficient �p = �.���. In the group of TC patients� who did not have the impact of IR in history �group II�� the individuals with genotype XPD Gln���Gln were not found. The tendency to increase the overall frequency of a�erra- tions in heterozygotes XPD Lys���Gln compared with carriers of genotype XPD Lys���Lys is insignificant in this group �p = �.�9�. However� TC patients without exposure to IR in history �group II� �eing homozygous XPD Lys���Lys carriers were characterized �y the significantly reduced frequency of chromosome-type a�errations �p = �.���� Ta�le ��. Sal’nikova et al. [��] revealed that frequency of spontaneous a�errations of chromosomal type additively increased �y rising the num�er of cop- ies of the minor allele variants of XPD *����G and *���A. These authors also o�served the elevated levels of γ-induced chromosome a�errations in car- riers of major alleles of XRCC1 G�99�A �Arg�99Gln� and XRCC1 *C��9T �Arg�94Trp� �p = �.���� and minor allele hOGG1 *C9��G �Ser���Cys� �p = �.���� [��]. Another study demonstrated the XPD Gln���Gln polymorphism association with increased levels of chromosomal a�errations in micronucleus test among radiologists and cardiologists� who carry out radiography [��� �4]. Au et al. [��] o�served that �y X-rays and UV �lood irradiation in volunteers� polymorphisms XPD ���Asn and XPD ���Gln were associated with increasing levels of chromatyd �reaks compared to wild-type alleles �p < �.���. Sal’nikova et al. found that frequency of spontaneous a�erra-found that frequency of spontaneous a�erra- tions of chromosomal type in the liquidators of the Chorno�yl accident increased in carriers of minor al- leles of the XPD gene �loci ����T>G and ���G>A� and “positive” genotypes of GSTM1-GSTT1 detoxification genes [��]. There was found the statistically significant increase of chromosomal a�errations in patients with lung cancer with polymorphic variants of the gene XPD T/G and G/G compared with T/T genotype [��]. In our study the carriage of homozygous minor allele XPD Gln���Gln of �NA repair gene was associated with increased levels of chromosomal insta�ility in TC pa- tients among evacuees and residents of contaminated areas. These patients� unlike the patients of the group IA� have �een su�jected to more prolonged exposure to the low doses of radiation. The results suggest a possi�le role for the violations of repair processes in the carriers of this genotype in the increased risk of TC development of cancer of the thyroid gland� especially in the conditions of chronic exposure to the low doses of radiation. Table 3. Link of repair gene polymorphisms XPD Lys751Gln with spontaneous level of chromosomal abnormalities in lymphocytes of peripheral blood in TC patients Groups, genotype Frequency of aberrant cell р Frequency of aberrations р Chromatyd-type aberrations р Chromosome-type aberrations р TC patients, group ІA (n = 10) Lys751Lys – – – – Lys751Gln 2.44 ± 0.91 2.79 ± 0.97 2.44 ± 0.91 0.35 ± 0.34 Gln751Gln 2.95 ± 0.72 p2 = 0.67 3.50 ± 0.78 p2 = 0.58 2.21 ± 0.63 p2 = 0.83 1.29 ± 0.48 p2 = 0.18 TC patients, group ІB (n = 22) Lys751Lys 3.00 ± 0.76 3.41 ± 0.81 2.20 ± 0.65 1.20 ± 0.48 Lys751Gln 2.68 ± 0.34 р3 > 0.05 3.07 ± 0.36 р3 > 0.05 1.73 ± 0.27 р3 > 0.05 1.34 ± 0.24 р3 > 0.05 Gln751Gln 4.51 ± 1.10 р1 = 0.24 р2 = 0.05 5.35 ± 1.19 р1 = 0.16 р2 = 0.03 3.10 ± 0.91 р1 = 0.41 р2 = 0.08 2.25 ± 0.78 р1 = 0.23 р2 = 0.18 TC patients, group ІІ (n = 10) Lys751Lys 1.85 ± 0.49 1.98 ± 0.50 1.85 ± 0.49 0.13 ± 0.13 Lys751Gln 2.49 ± 0.57 р3 = 0.40 3.04 ± 0.63 р3 = 0.19 1.52 ± 0.45 р3 = 0.62 1.52 ± 0.45 р3 = 0.007 Gln751Gln – – – – Notes: р1 — Gln751Gln vs Lys751Lys; р2 — Gln751Gln vs Lys751Gln; р3 — Lys751Gln vs Lys751Lys. ��� Experimental Oncology ��� �������� ���� ��ecem�er� It is not possi�le to estimate the influence of the a�er rations frequency on the modification of the TC risk in the carriers of the Gln���Gln genotype� �ecause in the Chorno�yl NPP accident liquidators of the group IА the genotype XPD Lys���Lys was not found. It should �e noted the significant reduction of the mitotic index of the lymphocyte culture in the group ІA patients in comparison with the other groups of patients. This resulted in the reduction of the fre- quency of a�errations in the total cell culture and the lack of the significant differences in the frequency of chromosomal a�errations �etween the carriers of the different genotypes in this group� compared with group IB. CONCLUSIONS In homozygous carriers of the minor allele of the gene XPD Gln���Gln� exposed to IR� there was found a signifi- cantly increased risk of TC with OR = �.��� p = �.�� �9�% CI �.�4���.�4� compared to a control group of Ukrai- nian population. In TC patients who were evacuees and residents of the areas contaminated with radionuclides� homozygous carriage of the minor allele variants XPD Gln���Gln gene was associated with the increased levels of spontaneous chromosome a�errations. REFERENCES 1. Wu X, Gu J, Grossman HB, et al. 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