Molecular genetic determinants of arterial thrombosis in patients with thoracoabdominal malignant tumors

Abstract

Background. Acute ischemic cerebral circulation disorder and myocardial infarction occupy one of the first places among the causes of postoperative mortality in patients with malignant tumors of thoracoabdominal localization. The issue of the role of molecular genetic factors of cardiovascular risk in the development of these complications has not been resolved at present.Objective. To analyze the effect of polymorphisms of hemostasis system genes on the development of coronary artery and cerebral artery thrombosis in patients with malignant tumors of thoracoabdominal localization.Materials and methods. The study included 163 patients operated in the Oncological Department of Surgical Methods of Treatment No. 11 (Thoracic Oncology) of the N.N. Blokhin National Medical Research Center of Oncology in 2018-2019. Two study groups consisted of patients with myocardial infarction (n = 62) and ischemic stroke (n = 24) in the perioperative period or in the anamnesis. The data of patients with a history of both myocardial infarction and ischemic stroke (n = 4) were taken into account in both groups. The control group (n = 81) included patients who had no severe concomitant cardiovascular pathology, including a family history. A molecular genetic study to determine polymorphisms of the genes of the hemostasis system was performed in the Laboratory of Clinical Oncogenetics of the N.N. Blokhin National Medical Research Center of Oncology using the reagents “Cardiogenetics of Thrombophilia” (DNA Technology LLC, Russia; RU No. FSR 2010/08414 dated 11/22/2016).Results. In patients with malignant tumors of thoracoabdominal localization who have suffered a myocardial infarction, in comparison with patients without cardiovascular pathology, a statistically significant difference in the frequency of carriage of homozygous variants of the genes FGB (χ2 = 8.18, p = 0.005), ITGA2 (χ2 = 9.48, p = 0.003), PAI-1 (χ2 = 4.45, p = 0.035), heterozygous forms of genes F5 (χ2 = 4.0, p = 0.046), ITGA2 (χ2 = 14.72, p <0.001), ITGB3 (χ2 = 4.28, p = 0.039), as well as the total frequency of genetic aberrations in these genes. In the group of patients who suffered an ischemic stroke, a statistically significant difference was determined relative to the control group in the frequency of carriage of the heterozygous variant of the mutation in the F2 gene (χ2 = 6.881, p = 0.009), the homozygous form of the mutation of the ITGA2 gene (χ2 = 15.724, p <0.001), the heterozygous variant of the mutation in the ITGB3 gene (χ2 = 3.861, p = 0.05), as well as the total frequency of carrying mutations in these genes. The study did not obtain a significant difference in the studied and control groups with respect to the frequency of polymorphism carriers G/A of the F7 gene (coagulation factor VII) and G/T of the F13 gene (coagulation factor XIII) associated with a reduced risk of thrombotic conditions. In all patients who had a myocardial infarction, and in 91.7 % of cases, several procoagulant polymorphisms were noted in the genotype of patients who had an ischemic stroke; in the group of patients without cardiovascular diseases, this indicator was 53 %, the difference in the groups was statistically significant (χ2 = 39.61, p <0.001; χ2 = 11.685, p <0.001, respectively).Conclusion. Based on the results of a molecular genetic study of factors associated with a high thrombogenic risk, a statistically significant difference in the frequency of occurrence of polymorphic markers F5 G1691A, FGB G(-455)A, ITGA2 C807T, ITGB3 T1565C, PAI-1 4G(-675)5G was revealed in patients with thoracoabdominal localization tumors who had suffered a myocardial infarction, and F2 G20210A, ITGA2 C807T, ITGB3 T1565C who had suffered an ischemic stroke, compared with cancer patients without concomitant cardiovascular pathology. The data of the conducted study make it possible to identify groups of oncological patients with increased risk of developing cardiovascular complications in the perioperative period and take additional measures to prevent thrombotic complications.