The role of polymorphic variants of the ERCC1 and ERCC2 genes in the development of gastric cancer in the Kyrgyz population

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Introduction. Gastric cancer is an aggressive malignant tumor of the gastrointestinal tract. Its onset and development are associated with genetic and external factors. Abnormalities in DNA repair genes, for example ERCC1 and ERCC2, can play a role in the development of this disease.

Aim. To determine prognostic significance of ERCC1 (rs11615, rs3212986) and ERCC2 (rs13181) gene polymorphisms in the development of gastric cancer in the Kyrgyz population.

Materials and methods. The study included 123 patients with malignant tumors of the stomach and 138 healthy individuals belonging to the Kyrgyz ethnic group. Genotyping was performed using allele-specific polymerase chain reaction. Statistical analysis included Fisher’s exact test and calculation of odds ratio (OR) for evaluation of associations between genotypes and clinical parameters. Genotyping results, histological and morphological tumor structures, patient age, tumor growth and location were compared using Fisher’s exact test. OR was determined through cross-tabulation.

Results. Statistically significant association of CC genotype of the ERCC1 (rs3212986) polymorphic locus with patient age (41–50 and 61–70 years) was found. Genotypes TG and TT of the ERCC2 (rs13181) gene were associated with poorly differentiated adenocarcinoma. Additionally, it was shown that CA genotype and A allele of the rs3212986 (ERCC1) polymorphism can play a protective role decreasing the likelihood of gastric cancer development in the Kyrgyz population (OR 0.472; 95 % confidence interval 0.287–0.785 and OR 0.676; 95 % confidence interval 0.464–0.991 for CC genotype and allele A, respectively) (р = 0.046).

Conclusion. Polymorphisms of the ERCC1 and ERCC2 genes can be associated with the risk of gastric cancer development in the Kyrgyz population. These data show the necessity of further studies investigating the role of these genes in gastric cancer and development of strategies for its prevention and treatment.

About the authors

Nurbek D. Bakirov

National Center of Oncology and Hematology, Ministry of Kyrgyz Republic

Author for correspondence.
Email: nurbek.bakirov.1977@mail.ru
ORCID iD: 0000-0002-0820-8987
SPIN-code: 1584-6430
Kyrgyzstan, Bld. 3, 92 Isa Akhunbayeva St., Bishkek 720064

Zh. T. Isakova

Kyrgyz National University named after Zhusup Balasagyn

Email: nurbek.bakirov.1977@mail.ru
ORCID iD: 0000-0002-3681-6939
Kyrgyzstan, 547 Frunze St., Bishkek 720033

V. N. Kipen

International Scientific and Educational Center for Innovative Medicine

Email: nurbek.bakirov.1977@mail.ru
ORCID iD: 0000-0002-7822-0746
Kazakhstan, 10 Alikhan Bokeikhan St., Astana 010000

A. K. Toygonbekov

National Center of Oncology and Hematology, Ministry of Kyrgyz Republic

Email: rbek.bakirov.1977@mail.ru
ORCID iD: 0000-0001-7937-2330
Kyrgyzstan, Bld. 3, 92 Isa Akhunbayeva St., Bishkek 720064

E. E. Omurbaev

National Center of Oncology and Hematology, Ministry of Kyrgyz Republic

Email: nurbek.bakirov.1977@mail.ru
ORCID iD: 0000-0002-8471-0813
Kyrgyzstan, Bld. 3, 92 Isa Akhunbayeva St., Bishkek 720064

R. A. Ramaldanov

National Center of Oncology and Hematology, Ministry of Kyrgyz Republic

Email: nurbek.bakirov.1977@mail.ru
ORCID iD: 0000-0002-0891-6123
Russian Federation, Bld. 3, 92 Isa Akhunbayeva St., Bishkek 720064

References

  1. Global Cancer Observatory. International Agency for Research on Cancer. Available at: https://gco.iarc.fr/today/.
  2. Theuer C.P. Asian gastric cancer patients at a southern California comprehensive cancer center are diagnosed with less advanced disease and have superior stage-stratified survival. Am Surg 2000;66:821–6.
  3. Schwarz R.E., Zagala-Nevarez K. Ethnic survival differences after gastrectomy for gastric cancer are better explained by factors specific for disease location and individual patient comorbidity. Eur J Surg Oncol 2002;28:214–9. doi: 10.1053/ejso.2001.1234
  4. Bisultanova Z.I., Bisultanova Z.R., Dzhambetova P.M. Analysis of polymorphic variants of excision repair genes in women with breast cancer in the Chechen population. Molekulyarnaya i prikladnaya genetika = Molecular and Applied Genetics 2016;21: 99–106. (In Russ.).
  5. Koshel A.P., Sevostyanov N.V., Klokov S.S. et al. The role of polymorphism of DNA excision repair genes and genes of xenobiotic biotransformation enzymes in early diagnosis of gastric cancer. Vestnik eksperimental’noy i klinicheskoy khirurgii = Bulletin of Experimental and Clinical Surgery 2010;3(4):339–43. (In Russ.).
  6. Georgiev G.P. Molecular-genetic mechanisms of tumor progression. Sorosovskiy obrazovatel’ny zhurnal (biologiya) = Soros Educational Journal (Biology) 2000:11:17–22. (In Russ.).
  7. Imyanitov E.N., Kalinovsky V.P., Knyazev P.G. Molecular genetics of human tumors. Voprosy onkologii = Issues of Oncology 1997;43(2): 95–101. (In Russ.).
  8. Semetey K.A., Makimbetov E.K., Isakova Zh.T., Kudaibergenova I.O. et al. Association of XRCC1, HMMR genes with the development of breast cancer in the Kyrgyz population. Zlokachestvennye opukholi = Malignant Tumors 2018;8(4):45–9. (In Russ.). doi: 10.18027/2224-5057-2018-8-4-45-49
  9. Benhmou S., Sarasin A. Variability in nucleotide excision repair and cancer risk: a review. Mutat Res 2000;462(2–3):149–58. doi: 10.1016/s1383-5742(00)00032-6
  10. Rechkunova N.I., Krasikova Yu.S., Lavrik O.I. Interactome of base and nucleotide repair systems. Molekulyarnaya biologiya = Molecular Biology 2021;55(2):181–93. (In Russ.). doi: 10.31857/S0026898421020129
  11. Shokrzadeh M., Mohammadpour A., Tabari Y., Almani S. Investigating the distribution of ERCC2 (rs13181) gene polymorphism in gastric cancer patients in mazandaran: a case-control study. J Genet Resour 2017;3(1):54–60. doi: 10.22080/jgr.2018.13345.1078
  12. Zhang J., Gu S.Y., Zhang P. et al. ERCC2 Lys751Gln polymorphism is associated with lung cancer among Caucasians. Eur J Cancer 2010;46:2479–84. doi: 10.1016/j.ejca.2010.05.008
  13. Zhou C.X., Zhao J.H. Systematic review on the association between ERCC1 rs3212986 and ERCC2 rs13181 polymorphisms and glioma risk. Genet Mol Res 2015;14(1):2868–75. doi: 10.4238/2015.March.31.17
  14. Shaposhnikov M.V., Proshkina E.N., Shilova L.A., Moskalov A.A. The role of DNA damage repair in longevity. Moscow, 2015. 164 p. (In Russ.).
  15. Edwards B.K., Noone A.M., Mariotto A.B. et al. Annual report to the nation on the status of cancer, 1975–2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 2014;120:1290–314. doi: 10.1002/cncr.28509
  16. De Majo F., Martens L., Hegenbarth J. et al. Genomic instability in the naturally and prematurely aged myocardium. Proc Natl Acad Sci USA 2021;118(36):E2022974118. doi: 10.1073/pnas.2022974118
  17. Mahmoudi M., Mercer J., Bennett M. DNA damage and repair in atherosclerosis. Cardiovasc Res 2006;71(2):259–68. doi: 10.1016/j.cardiores.2006.03.002
  18. Giachino D.F., Ghio P., Regazzoni S. et al. Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer. Clin Cancer Res 2007;13(10):2876–81. doi: 10.1158/1078-0432.CCR-06-2543
  19. Khalouei A., Masoumi-Ardakani Y., Jafarzaheh A. et al. Association of ERCC1 gene polymorphisms (rs3212986 and rs11615) with the risk of lung cancer in a population from Southeast Iran. J Res Health Sci 2024;24(4):e00631. doi: 10.34172/jrhs.2024.166
  20. Boldrin E., Malacrida S., Rumiato E. et al. Association between ERCC1 rs3212986 and ERCC2/XPD rs1799793 and OS in patients with advanced esophageal cancer. Front Oncol 2019 Feb 21;9:85. doi: 10.3389/fonc.2019.00085
  21. Tang W., Wang H., Wang Y., Wang X. ERCC1 rs3212986 A/C polymorphism is not associated with chemotherapy treatment outcomes in gastric cancer patients: evidence from 11 publications in Chinese populations. Onco Targets Ther 2017;11:1–8. doi: 10.2147/OTT.S148214
  22. Adico M.D.W., Zouré A.A., Sombié H.K. et al. Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso. Mol Genet Genomic Med 2023;11(4):e2134. doi: 10.1002/mgg3.2134
  23. Bogush T.A., Popova A.S., Dudko E.A. et al. ERCC1 as a marker of ovarian cancer resistance to platinum drugs. Antibiotiki i khimioterapiya = Antibiotics and Chemotherapy 2015;60(3–4): 42–50. (In Russ.).

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2026 Bakirov N.D., Isakova Z.T., Kipen V.N., Toygonbekov A.K., Omurbaev E.E., Ramaldanov R.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-57560 от  08.04.2014.