Effect of VEGF gene polymorphism on the survival of a patient with non-small cell lung cancer
https://doi.org/10.29235/1561-8323-2024-68-3-220-228
Abstract
Currently, much attention is paid to studying the vascular endothelial growth factor (VEGF) that stimulates angiogenesis, as a potential target for antiangiogenic therapy. The purpose of this work was to study the effect of polymorphic variants rs2010963 (G-634C), rs699947 (A-2578C), and rs3025039 (C+936T) of the VEGF gene, encoding a vascular endothelial growth factor, on the overall (OS) and adjusted survival (AS) of patients with non-small cell lung cancer (NSCLC) at stages I–III. The effect of VEGF rs699947 polymorphic variants on the extent of tumor spread was shown. A connection between AS and polymorphic variants rs2010963 (G-634C) and rs699947 (A-2578C) was established. The one-year adjusted survival (AS) in the -634G/C genotype carriers was 81.9 ± 3.9 %; in the -634G/G genotype carriers – 92.8 ± 2.5 %; and p = 0.016 was the significance level. Two-year AS was as follows: in the carriers of the -634G/C genotype was 70.4 ± 4.6 %; in the carriers of the -634G/G genotype – 84.3 ± 3.5 %; and p = 0.015. Three-year AS: in the carriers of the -634G/ genotype C was 63.0 ± 4.9 %; in the carriers of the -634G/G genotype – 76.7 ± 4.1 %; and p = 0.029. One-year and two-year AS in the carriers of the -2578A/A genotype was significantly higher than in the carriers of the -2578C/C genotype (p = 0.015 and p = 0.042 respectively). The identified influence of the polymorphic variants rs2010963 and rs699947 on the survival of NSCLC patients during the first three years after the established diagnosis shows a need to use knowledge about the genetic characteristics of a tumor during therapy.
About the Authors
M. N. Shapetska
Belarusian State Medical University
Belarus
Belarus
Shapetska Michail N. – Ph. D. (Medicine), Assistant Professor
83, Dzerzhinsky Ave., 220116, Minsk
A. P. Mikhalenka
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus
Belarus
Belarus
Mikhalenka Alena P. – Ph. D. (Biology), Leading Researcher
27, Akademicheskaya Str., 220072, Minsk
A. N. Shchayuk
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus
Belarus
Belarus
Shchayuk Anna N. – Ph. D. (Biology), Senior Researcher
27, Akademicheskaya Str., 220072, Minsk
L. V. Mirilenko
N. N. Alexandrov National Cancer Centre
Belarus
Belarus
Mirilenko Ludmila V. – Ph. D. (Medicine), Assistant Professor
223040, Lesnoy, Minsk region
L. V. Gorbatenko
Minsk City Clinical Oncology Center
Belarus
Belarus
Gorbatenko Ludmila V. – Resuscitator
64, Nezavisimosti Ave., 220013, Minsk
A. V. Kilchevsky
Institute of Genetics and Cytology of the National Academy of Sciences of Belarus
Belarus
Belarus
Kilchevsky Aleksandr V. – Academician, D. Sc. (Biology), Professor, Chief Researcher
27, Akademicheskaya Str., 220072, Minsk
References
1. Sung H., Ferlay J., Siegel R. L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 2021, vol. 71, no. 3, pp. 209–249. https://doi.org/10.3322/caac.21660
2. Allemani C., Matsuda T., Di Carlo V., Harewood R., Matz M., Nikšić M., Bonaventure A., Valkov M., Johnson C. J., Estève J., Ogunbiyi O. J., Azevedo e Silva G., Chen W. Q., Eser S., Engholm G., Stiller C. A., Monnereau A., Woods R. R., Visser O., Lim G. H., Aitken J., Weir H. K., Coleman M. P.; CONCORD Working Group. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, vol. 391, no. 1025, pp. 1023–1075. https://doi.org/10.1016/S0140-6736(17)33326-3
3. Folkman J. Angiogenesis: an organizing principle for drug discovery? Nature Reviews Drug Discovery, 2007, vol. 6, pp. 273–286. https://doi.org/10.1038/nrd2115
4. Carmeliet P., Jain R. K. Molecular mechanisms and clinical applications of angiogenesis. Nature, 2011, vol. 473, pp. 298–307. https://doi.org/10.1038/nature10144
5. Olsson A. K., Dimberg A., Kreuger J., Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nature Reviews Molecular Cell Biology, 2006, vol. 7, pp. 359–371. https://doi.org/10.1038/nrm1911
6. Mathew C. C. The isolation of high molecular weight eucaryotic DNA. Walker J. M. N. J., ed. Methods in Molecular Biology: Nucleic Acids. Clifton, 1984, vol. 2, pp. 31–34. https://doi.org/10.1385/0-89603-064-4:31
7. Shapetska M. N., Shchayuk A. N., Mikhalenko E. P., Chebotareva N. V., Pisarchik S. N., Krupnova E. V. Clinical and morphological characteristics of NSCLC and VEGF gene polymorphism. International Journal of Advanced Research, 2016, vol. 4, pp. 1802–1813. https://doi.org/10.21474/ijar01/1657
8. Langsenlehner U., Hofmann G., Renner W., Gerger A., Krenn-Pilko S., Thurner E.M., Krippl P., Langsenlehner T. Association of vascular endothelial growth factor – A gene polymorphisms and haplotypes with breast cancer metastases. Acta Oncology, 2015, vol. 54, no. 3, pp. 368–376. https://doi.org/10.3109/0284186x.2014.948056
9. Han S. W., Kim G. W., Seo J. S., Kim S. J., Sa K. H., Park J. Y., Lee J., Kim S. Y., Goronzy J. J., Weyand C. M., Kang Y. M. VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology (Oxford), 2004, vol. 43, no. 9, pp. 1173–1177. https://doi.org/10.1093/rheumatology/keh281
10. Shahbazi M., Fryer A. A., Pravica V., Brogan I. J., Ramsay H. M., Hutchinson I. V., Harden P. N. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. Journal of the American Society of Nephrology, 2002, vol. 13, no. 1, pp. 260–264. https://doi.org/10.1681/asn.v131260
11. Renner W., Kotschan S., Hoffmann C., Obermayer-Pietsch B., Pilger E. A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. Journal of Vascular Research, 2000, vol. 37, no. 6, pp. 443–448. https://doi.org/10.1159/000054076
12. Lee D., Hwang S. G., Kim J., Choe J. Functional interaction between p/CAF and human papillomavirus E2 protein. Journal of Biological Chemistry, 2002, vol. 277, no. 8, pp. 6483–6489. https://doi.org/10.1074/jbc.m105085200
13. Nefedova N. A., Kharlova O. A., Danilova N. V., Malkov P. G., Gaifullin N. M. Markers of angiogenesis in tumor growth. Arkhiv Patologii, 2016, vol. 78, no. 2, pp. 55–62 (in Russian). https://doi.org/10.17116/patol201678255-62
14. Tyczyńska M., Kędzierawski P., Karakuła K., Januszewski J., Kozak K., Sitarz M., Forma A. Treatment Strategies of Gastric Cancer-Molecular Targets for Anti-angiogenic Therapy: a State-of-the-art Review. Journal of Gastrointestinal Cancer, 2021, vol. 52, pp. 476–488. https://doi.org/10.1007/s12029-021-00629-7
15. Allegra C. J., Yothers G., O’Connell M. J., Sharif S., Petrelli N. J., Colangelo L. H., Atkins J. N., Seay T. E., Fehrenbacher L., Goldberg R. M., O’Reilly S., Chu L., Azar C. A., Lopa S., Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. Journal of Clinical Oncology, 2011, vol. 29, no. 1, pp. 11–16. https://doi.org/10.1200/jco.2010.30.0855
16. Bergers G., Hanahan D. Modes of resistance to anti-angiogenic therapy. Nature Reviews Cancer, 2008, vol. 8, pp. 592–603. https://doi.org/10.1038/nrc2442
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