Biology of telomeres and geomic instability in the pathogenesis of lung cancer with cardiovascular pathology

Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer death worldwide. Genomic instability is an important feature of almost all human cancers. Cardiovascular disease and cancer share modifiable risk factors, pathophysiological mechanisms, and mutual contributions to genomic instability. Cardiovascular disease and cancer have common modifiable risk factors, pathophysiological mechanisms and mutual contributions to genomic instability. 80 men with lung cancer were examined. The control group included 100 men without oncopathology of close age, living in the same area. A micronucleus assay was performed on blood lymphocytes. The length of DNA telomeric regions was estimated using a quantitative polymerase reaction. An increase in the frequency of occurrence of markers of cytogenetic disorders in patients with lung cancer was noted. In the lymphocytes of the control group, a higher level of indicators of the proliferative pool, the replication index, was registered. The relative telomere length of people in the control group is 1.6 times shorter than the telomere length of patients with lung cancer. In patients with lung cancer and concomitant coronary heart disease, differences in the incidence of apoptosis from similar genotoxic parameters in patients without cardiovascular disease were found. The hTERT gene was not expressed.

1. International Agency for Research on Cancer. Global Cancer Observatory: cancer today. World Health Organization. https://gco.iarc.fr/today,2020.

2. Howlader N., Forjaz G., Mooradian M.J., et al. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383:640–649. doi: 10.1056/NEJMoa1916623.

3. Inohara T., Endo A., Melloni C. Unmet needs in managing myocardial infarction in patients with malignancy. Front Cardiovasc Med. 2019;6:57. doi: 10.3389/fcvm.2019.00057.

4. Li L., Zhang X., Tian T., Pang L. Mathematical modelling the pathway of genomic instability in lung cancer. Sci Rep. 2019;9(1):14136. doi: 10.1038/s41598-019-50500-w.

5. Salakhov R.R., Ponasenko A.V. Dlina telomer i serdechno-sosudistyye zabolevaniya [Telomere length and cardiovascular diseases]. Kompleksnyye problemy serdechno-sosudistykh zabolevaniy [Complex Issues of Cardiovascular Diseases]. 2018;7(4S):101-107. (In Russ). doi: 10.17802/2306-1278-2018-7-4S-101-107

6. Fenech M., Knasmueller S., Bolognesi C., et al. Micronuclei as bio-markers of DNA damage, aneuploidy, inducers of chromosomal hypermutation and as sources of pro-inflammatory DNA in humans. Mutat Res Rev Mutat Res. 2020;786:108342. doi: 10.1016/j.mrrev.2020.108342

7. El-Zein R.A., Lopez M.S., D’Amelio A.M.Jr. et al. The cytokinesis-blocked micronucleus assay as a strong predictor of lung cancer: extension of a lung cancer risk prediction model. Cancer Epidemiol. Biomarkers Prev. 2014;23(11):2462–2470. doi: 10.1158/1055-9965. EPI-14-0462.

8. Chazova I.E., Oschepkova E.V., Kantorova A.Yu. Komorbidnost’ serdechno-sosudistykh i onkologicheskikh zabolevaniy: problemy diagnostiki kardiotoksicheskikh effektov khimio- i luchevoy terapii [Comorbidity of cardiovascular diseases and cancers: Problems in the diagnosis of cardiotoxic effects of chemo- and radiation therapy]. Terapevticheskii Arkhiv [Therapeutic archive]. 2015;87(9):4-10. (In Russ.). doi: 10.17116/terarkh20158794-10.

9. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. doi: 10.3322/caac.21590.

10. Zhang T., Joubert P., Ansari-Pour N., et al. Genomic and evolutionary classification of lung cancer in never smokers. Nat Genet. 2021;53(9):1348-1359. doi: 10.1038/s41588-021-00920-0.

11. Barrera G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol. 2012;2012:137289. doi: 10.5402/2012/137289.

12. Zito Marino F., Bianco R., Accardo M., et al. Molecular heterogeneity in lung cancer: from mechanisms of origin to clinical implications. Int J Med Sci. 2019;16(7):981-989. doi: 10.7150/ijms.34739.

13. Hamada T., Yuan C., Bao Y., et al. Prediagnostic Leukocyte Telomere Length and Pancreatic Cancer Survival. Cancer Epidemiol Bio-markers Prev. 2019;28(11):1868-1875. doi: 10.1158/1055-9965.EPI-19-0577

14. Asanov M.A., Sinitsky M.Y., Ponasenko A.V., Minina V.I. Genomnaya nestabil’nost’ limfotsitov u bol’nykh rakom legkogo s soputstvuyushchey ishemicheskoy bolezn’yu serdtsa [Genomic instability of lymphocytes in patients with lung cancer with combined ischemic heart disease]. Geny i kletki [Genes and Cells]. 2021;16(2):61-65. (In Russ.). doi:10.23868/202107007.

15. Liu G., Pei F., Yang F., Li L., et al. Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer. Int J Mol Sci. 2017;18(2):367. doi: 10.3390/ijms18020367.

16. Qian Y., Ding T., Wei L., et al. Shorter telomere length of T-cells in peripheral blood of patients with lung cancer. Onco Targets Ther. 2016;4(9):2675-2682. doi: 10.2147/OTT.S98488.

17. Druzhinin V.G., Baranova E.D., Volobaev V.P., et al. The length of telomeres and the baseline level of cytogenetic damage in leukocytes of lung cancer patients. Russian Journal of Genetics. 2022; 58(1): 73-84. doi: 10.31857/S0016675822010027.

18. Aviv A., Anderson J.J., Shay J.W. Mutations, Cancer and the Telomere Length Paradox. Trends Cancer. 2017;3(4):253-258. doi: 10.1016/j.trecan.2017.02.005.

19. Counter C.M., Gupta J., Harley C.B., et al. Telomerase activity in normal leukocytes and in hematologic malignancies. Blood. 1995;85(9):2315-2320

20. The Genotype-Tissue Expression (GTEx) project. Доступ по ссылке: https://gtexportal.org

21. Park G.M., Lee J.H., Lee S.W., et al. Comparison of coronary computed tomographic angiographic findings in asymptomatic subjects with versus without diabetes mellitus. Am J Cardiol. 2015;116(3):372-378. doi: 10.1016/j.amjcard.2015.04.046.

22. Andreassi M.G., Barale R., Iozzo P., et al. The association of micro-nucleus frequency with obesity, diabetes and cardiovascular disease. Mutagenesis. 2011;26(1):77-83. doi: 10.1093/mutage/geq077.

23. Deavall D.G., Martin E.A., Horner J.M., et al. Drug-induced oxidative stress and toxicity. J Toxicol. 2012;2012:645460. doi: 10.1155/2012/645460.