mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2024.022Vmes-60Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕORIGINAL RESEARCHВлияние полиморфизма в генах антиоксидантов на риск развития злокачественных новообразований у облученных людейThe impact of polymorphisms in antioxidant genes on the risk of malignant neoplasm development in exposed individualsБлиноваЕ. А.BlinovaE. A.

Евгения Андреевна Блинова

ул. Воровского, д. 68, корп. А, г. Челябинск, 454141

Eugenia A. Blinova

Vorovsky, 68-А, Chelyabinsk, 454141

blinova@urcrm.ruКореченковаА. В.KorechenkovaA. V.

ул. Воровского, д. 68, корп. А, г. Челябинск, 454141

Vorovsky, 68-А, Chelyabinsk, 454141

ЯнишевскаяМ. А.YanishevskayaM. A.

ул. Воровского, д. 68, корп. А, г. Челябинск, 454141

Vorovsky, 68-А, Chelyabinsk, 454141

АклеевА. В.AkleyevA. V.

ул. Воровского, д. 68, корп. А, г. Челябинск, 454141

Vorovsky, 68-А, Chelyabinsk, 454141

Уральский научно-практический центр радиационной медицины Федерального медико-биологического агентстваРоссияUrals Research Center for Radiation Medicine of the Federal Medical Biological AgencyRussian Federation2024231020242624955Copyright © Блинова Е.А., Кореченкова А.В., Янишевская М.А., Аклеев А.В., 20242024Блинова Е.А., Кореченкова А.В., Янишевская М.А., Аклеев А.В.Blinova E.A., Korechenkova A.V., Yanishevskaya M.A., Akleyev A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/60

На фоне дополнительного радиационного воздействия однонуклеотидные полиморфизмы в генах, кодирующих ферменты антиоксидантной системы, могут способствовать усилению окислительного стресса, возникновению повреждений ДНК и, как следствие, приводить к повышению риска развития злокачественных новообразований (ЗНО). Целью работы было установить связи полиморфных локусов СYBA (rs4673), GPX1 (rs1050450), MPO (rs2333227), CAT (rs7943316), SOD2 (rs4880) с риском развития ЗНО у лиц, подвергшихся хроническому низкоинтенсивному радиационному воздействию, с учетом межгенных взаимодействий и дозы радиационного облучения. В исследование были включены две группы людей: облученные лица без ЗНО — 384 человека со средней накопленной дозой облучения красного костного мозга (ККМ) 796,95 ± 35,97 мГр; облученные лица с ЗНО в анамнезе — 227 человек со средней накопленной дозой облучения ККМ 520,06 ± 38,72 мГр. Амплификацию полиморфных локусов rs4880, rs2333227, rs7943316, rs4673, rs1050450 проводили методом ПЦР в реальном времени. Для всех полиморфных участков генов выявлено соответствие равновесию Харди–Вайнберга. Обнаружено, что аллели rs4880*С (SOD2) и rs1050450*Т (GPX1) ассоциированы с повышенным риском развития ЗНО согласно доминантной (ОШ = 1,49 (1,02–2,18), р = 0,04) и рецессивной (ОШ = 2,00 (1,11–3,62), р = 0,02) моделям наследования соответственно. Получена модель межфакторных взаимодействий со 100%-й воспроизводимостью и точностью 66% (р = 0,001), включающая в себя полиморфизмы SOD2 (rs4880), СYBA (rs4673) и фактор накопленной дозы облучения ККМ. Таким образом, полиморфные локусы генов, регулирующих оксидантный статус клеток, связаны с повышенным риском развития ЗНО у лиц, подвергшихся хроническому радиационному воздействию с преимущественным облучением ККМ.

In the context of additional radiation exposure, single nucleotide polymorphisms in the genes encoding the antioxidant system enzymes can contribute to the oxidative stress enhancement, damage to DNA, and therefore lead to the increase in the risk of malignant neoplasm (MN) development. The study was aimed to determine the association of the СYBA (rs4673), GPX1 (rs1050450), MPO (rs2333227), CAT (rs7943316), SOD2 (rs4880) polymorphic loci with the risk of MN development in individuals affected by low dose rate chronic radiation exposure considering intergenic interactions and the radiation dose. Two groups of individuals were included in the study: exposed individuals with no MNs — 384 people with the mean accumulated dose to the red bone marrow (RBM) of 796.95 ± 35.97 mGy; exposed individuals with the history of MNs — 227 people with the mean accumulated dose to RBM of 520.06 ± 38.72 mGy. Amplification of the rs4880, rs2333227, rs7943316, rs4673, rs1050450 polymorphic loci was performed with real time PCR. Compliance with the Hardy–Weinberg equilibrium was reported for all gene polymorphisms. It has been found that the rs4880*С (SOD2) and rs1050450*Т (GPX1) alleles are associated with the risk of MN development in accordance with the dominant (OR = 1.49 (1.02–2.18), р = 0.04) and recessive (OR = 2.00 (1.11–3.62), р = 0.02) inheritance modes, respectively. An interfactor interaction model with the 100% reproducibility and 66% accuracy (р = 0.001) has been obtained that includes the SOD2 (rs4880), СYBA (rs4673) polymorphisms and the factor of accumulated dose to RBM. Thus, polymorphic loci of the genes regulating the oxidative status of the cells are associated with the increased risk of MN development in individuals, who have experienced chronic radiation exposure with predominant exposure of RBM.

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The authors declare that there are no conflicts of interest present.