oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2023-22-1-66-73oncotomsk-2432Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESМолекулярно-генетические факторы риска развития ишемического инсульта у больных злокачественными опухолями торакоабдоминальной локализацииMolecular genetic risk factors for ischemic stroke in patients with thoracoabdominal malignant tumorshttps://orcid.org/0000-0001-8501-7917КоролёваА. А.KorolyovaA. A.

Королёва Анна Анатольевна, аспирант онкологического отделения хирургических методов лечения № 11 (торакальной онкологии) НИИ клинической онкологии им. Н.Н. Трапезникова

115448, г. Москва, Каширское шоссе, 23

Anna A. Korolyova, Postgraduate, Oncology Department of Surgical Methods of Treatment № 11 (Thoracic Oncology)

23, Kashirskoe shosse, 115448, Moscow

anna.korolyova@hotmail.comhttps://orcid.org/0000-0002-0833-6452ГерасимовС. С.GerasimovS. S.

Герасимов Сергей Семенович, доктор медицинских наук, старший научный сотрудник онкологического отделения хирургических методов лечения № 11 (торакальной онкологии) НИИ клинической онкологии им. Н.Н. Трапезникова

115448, г. Москва, Каширское шоссе, 23

Sergey S. Gerasimov, MD, DSc, Senior Researcher, Oncology Department of Surgical Methods of Treatment № 11 (Thoracic Oncology)

23, Kashirskoe shosse, 115448, Moscow

ЛюбченкоЛ. Н.LyubchenkoL. N.

Любченко Людмила Николаевна, доктор медицинских наук, заведующая отделом молекулярной генетики и клеточных технологий

125284, г. Москва, 2-й Боткинский пр-д, 3

SPIN-код: 9589-9057

Liudmila N. Lyubchenko, MD, DSc, Head of the Department of Molecular Genetics and Cell Technologies

3, 2nd Botkinsky proezd, 125284, Moscow

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the RussiaRussian FederationМосковский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияMoscow P.A. Hertzen Cancer Research Center – branch of National Medical Research Center of Radiology of the Ministry of Health of RussiaRussian Federation2023220220232216673Copyright © Королёва А.А., Герасимов С.С., Любченко Л.Н., 20232023Королёва А.А., Герасимов С.С., Любченко Л.Н.Korolyova A.A., Gerasimov S.S., Lyubchenko L.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2432Актуальность

Актуальность. Ишемический инсульт занимает одно из первых мест среди причин послеоперационной летальности у больных злокачественными опухолями торакоабдоминальной локализации. В настоящее время не решен вопрос о роли молекулярно-генетических факторов сердечно-сосудистого риска в развитии данного осложнения у онкологических пациентов. Выявление генетических детерминант артериального тромбоза позволит прогнозировать повышенный риск развития ишемического инсульта и создаст возможность патогенетически обоснованной его профилактики среди носителей генетических маркеров тромбофилии.

Цель исследования ‒ сравнить частоту носительства прокоагулянтных мутаций в генах системы гемостаза у онкологических больных, перенесших ишемический инсульт, и у онкологических пациентов без сопутствующих сердечно-сосудистых заболеваний.

Материал и методы

Материал и методы. В нерандомизированное обсервационное пилотное исследование включено 105 больных злокачественными опухолями торакоабдоминальной локализации, оперированных в онкологическом отделении хирургических методов лечения № 11 (торакальной онкологии) торакоабдоминального отдела ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» в 2018–19 гг. Исследуемую группу составили 24 пациента с перенесенным ишемическим инсультом в анамнезе или в периоперационном периоде. В контрольную группу включен 81 больной без сопутствующих сердечно-сосудистых заболеваний, в том числе в семейном анамнезе. Молекулярногенетическое исследование с целью определения полиморфизмов генов системы гемостаза выполнено методом полимеразной цепной реакции в режиме реального времени.

Результаты

Результаты. У пациентов, перенесших ишемический инсульт, в сравнении с больными без сердечно-сосудистой патологии определена статистически значимая разница в частоте носительства гетерозиготного варианта (GA) мутации в гене F2 (c2=6,881, p=0,009), гомозиготной формы (TT) мутации гена ITGA2 (c2=15,724, p<0,001), гетерозиготного варианта (TC) мутации в гене ITGB3 (c2=3,861, p=0,05), а также общей частоте носительства генетических аберраций в указанных генах.

Заключение

Заключение. По результатам проведенного генотипирования факторов, ассоциированных с высоким тромбогенным риском, выявлена статистически достоверная разница в частоте встречаемости полиморфизмов генов F2, ITGA2, ITGB3 у больных злокачественными опухолями торакоабдоминальной локализации, перенесших ишемический инсульт, по сравнению с онкологическими пациентами без сердечно-сосудистых заболеваний. Роль генетического фактора в развитии ишемического инсульта у онкологических пациентов требует дальнейшего изучения.

Background

Background. Ischemic stroke is one of the most frequent causes of postoperative death in patients with thoracoabdominal malignant tumors. The role of molecular genetic factors of cardiovascular risk in the development of this complication in cancer patients has not yet been studied properly. The identification of genetic determinants of arterial thrombosis will allow predicting an increased risk of ischemic stroke and will create the possibility of pathogenetically justified prevention among carriers of genetic markers of thrombophilia.

Aim

Aim. To compare the frequency of carriage of procoagulant mutations in the genes of the hemostasis system in cancer patients who have suffered an ischemic stroke and in cancer patients without concomitant cardiovascular diseases.

Material and Methods

Material and Methods. The non-randomized observational pilot research included 105 patients with thoracoabdominal tumors treated at the Thoracoabdominal Department of N. N. Blokhin National Research Center of Oncology during the period 2018–2019. The study group (n=24) consisted of patients with a history of ischemic stroke or perioperative stroke. The control group (n=81) included patients without concomitant cardiovascular diseases, including a family history. The real time polymerase chain reaction technique was used to determine the gene polymorphisms of blood coagulation.

Results

Results. We found a statistically significant difference in the frequency of carriage of the heterozygous variant (GA) mutation of the F2 gene (c2=6,881, p=0,009), homozygous mutation (TT) of the of the ITGA2 gene (c2=15,724, p<0,001), the heterozygous variant (TC) mutation of the ITGB3 gene (c2=3,861, p=0,05) as well as the general frequency of genetic aberrations in these genes between patients with thoracoabdominal malignant tumors, who had ischemic stroke and patients with thoracoabdominal malignant tumors without cardiovascular pathology.

Conclusion

Conclusion. Based on the results of the genotyping of factors associated with a high thrombogenic risk, a statistically significant difference in the frequency of occurrence of polymorphisms of hemostasis system genes F2, ITGA2, ITGB3 was revealed between patients with thoracoabdominal malignant tumors, who had ischemic stroke and those without cardiovascular diseases. The role of the genetic factor in the development of ischemic stroke in cancer patients requires further study.

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