Over the past decades, there were many reports of an increase in the number of thyroid cancer patients among those, who were exposed to ionizing radiation as a result of the Chernobyl disaster. The purpose of the study was to determine the features of DNA repair genes XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in patients with thyroid cancer (TC), who were exposed to ionizing radiation (IR) as a result of the Chernobyl disaster. Material and methods. For molecular genetic studies 102 patients with thyroid cancer were selected: 38 patients, who were exposed to ionizing radiation due to Chernobyl (I group) and 64 patients without experience of ionizing radiation exposure (II group). There were two subgroups among 38 patients with the experience of radiation exposure: IA group had 10 patients who were clean–up workers at the Chernobyl nuclear power plant; and IB group included 28 patients who were evacuees and residents from areas contaminated with radionuclides. Genomic DNA was extracted of peripheral blood mononuclear cells using DNA isolation kit NeoPrep DNA Magnet (Neogene, Ukraine) according to the manufacturer's instructions. PCR was performed in a final volume of 20 ml, containing approximately 20 ng of DNA studied, 10.0 pmol of each primer, using the buffer provided by the manufacturer. Determination of the dose load was carried out in groups of patients with experience of radiation exposure. The average dose of external irradiation in the group of clean–up workers was 45,5 ± 3,92 mSv. The average dose of external exposure in the group of evacuees was 7,2 ± 0,4 mSv. Results and discussion. In the analysis of the polymorphism of the DNA repair genes XRCC1 and XPD in patients with radiation–associated and spontaneous thyroid cancer, certain features were identified. In the total group of thyroid cancer patients, regardless their experience of radiation exposure, the distribution of genotypes corresponded to Hardy–Weinberg equation. When compared with a control group of Ukrainian population in homozygous carriers of the minor allele of the gene XPD Lys751Gln, exposed to IR (I group), we found a significantly increased risk of thyroid cancer: OR = 3.66, p = 0.02 (CI 95% 1.20–14.65). Comparing with the literature data, the association of polymorphism of the gene XPD Lys751Gln with the risk of developing radiation–associated and spontaneous thyroid cancer was not detected. When compared to the literature data on XRCC1 polymorphisms in radiation–exposed individuals without cancer pathology, which we used as a control group, the risk of thyroid cancer in carriers of homozygous minor allele Gln399Gln XRCC1 gene, in people exposed to the IR (I group), in our study was significantly high: OR = 4,17, p = 0,001. Comparing with the control group of the Ukrainian population we did not detect association of polymorphism of the gene XRCC1 Arg399Gln with the risk of development radiation–associated and spontaneous thyroid cancer. Conclusion. For the first time in Ukraine the frequencies of polymorphic alleles of DNA repair genes XPD Lys751Gln and XRCC1 Arg399Gln in patients with thyroid cancer, who were exposed to ionizing radiation due to Chernobyl accident (0.49 and 0.57, respectively) and in patients with thyroid cancer without affecting IR in their life (0.39 and 0.37, respectively) have been determined. The carriage of homozygous minor allele of DNA repair genes XRCC1 Gln399Gln and XPD Gln751Gln Gln751Gln is a risk factor of development thyroid cancer under the influence of ionizing radiation in the study group of the Ukrainian population and may be the basis for forming a risk group for the predisposition to develop radiation–associated cancer pathology of the thyroid gland.
Keywords: Chernobyl disaster, ionizing radiation, polymorphism of DNA repair genes XRCC1, XPD, thyroid cancer; clean–up workers
Full text: PDF (Ukr) 238K