Contribution of the genetic polymorphisms to cancer risk in chronically exposed individuals
https://doi.org/10.21514/1998-426X-2025-18-3-7-17
Abstract
The objective of the current research is to evaluate the contribution of the genetic factor to the risk of cancer development in the individuals affected by chronic low dose-rate exposure on the Techa River. Materials and Methods: The study of the relationship between the polymorphic loci of the genes regulating cell cycle and apoptosis with the risk of cancer development involved 922 members of the Southern Urals Population Exposed to Radiation cohort. Real-time PCR was used to perform the genotyping of polymorphic loci. Results and Discussion: A statistically significant relationship of the alleles rs2279744*С of the gene MDM2 and rs2279115*С of the gene BCL-2 with the increased risk of cancer development has been established (odds ratio = 1.75; confidence interval 95 % [1.15-2.65]; p=0.008 and odds ratio = 1.63; confidence interval 95 % [1.21-2.21]; p=0.001 respectively). Single nucleotide polymorphism that is associated with a decreased risk of cancer development has also been revealed: the allele rs1801270*А of the gene CDKN1A (odds ratio = 0.62; confidence interval 95 % [0.44-0.88]; p=0.007). The analysis of gene interaction factor and absorbed dose to the red bone marrow determined the most statistically significant model that includes the dose to the red bone marrow, NFkB rs28362491, ATM rs664677, BCL2 rs2279115, MDM2 rs2279744 (repeatability is 10 out of 10, accuracy 62 %; p=0.04). Polymorphism rs2279744 of the gene MDM2 is the greatest information contributor (2.43 %). Conclusion: Single nucleotide polymorphisms of the genes encoding cell cycle and cell death enzymes are capable of modifying cancer development risk.
About the Authors
E. A. BlinovaRussian Federation
Evgenia A. Blinova – Candidate of Science in Biology, Director - Chief Researcher of the Research Institute of Radiation Biology and Radiation Medicine
19, Ozyorskoe Shosse, Ozyorsk, Chelyabinsk Region, 456783
A. V. Korechenkova
Russian Federation
Anastasiya V. Korechenkova – Researcher of the Laboratory of Molecular and Cellular Radiobiology
Ozyorsk
A. V. Akleyev
Russian Federation
Alexander V. Akleyev – Doctor of Sciences in Medical Sciences, Professor, Honoured Worker of Science of the Russian Federation, Acting Director General
Ozyorsk
References
1. Bourguignon M, Blanchardon E, De Vathaire F, Bouffler S. Individual radiosensitivity: a key issue in radiation protection. International Journal of Low Radiation. 2013;9(1): 52–58. DOI: 10.1504/IJLR.2013.054186.
2. Yin J, Vogel U, Ma Y, Qi R, Sun Z, Wang H. The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population. Lung Cancer. 2007;56(2): 153–160. DOI: 10.1016/j.lungcan.2006.12.012.
3. Yen CY, Liu SY, Chen CH, Tseng HF, Chuang LY, Yang CH, et al. Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan. Journal of Oral Pathology and Medicine. 2008;37(5): 271–277. DOI: 10.1111/j.1600-0714.2007.00608.x.
4. Xue X, Yin Z, Lu Y, Zhou B, Duan X, Zhang Z, et al. The joint effect of hOGG1, APE1, and ADPRT polymorphisms and cooking oil fumes on the risk of lung adenocarcinoma in Chinese non-smoking females. PLoS One. 2013;8(8): e71157. DOI: 10.1371/journal.pone.0071157.
5. Willems P, Claes K, Baeyens A, Vandersickel V, Werbrouck J, De Ruyck K, et al. Polymorphisms in nonhomologous end-joining genes associated with breast cancer risk and chromosomal radiosensitivity. Genes Chromosomes Cancer. 2008;47(2): 137–148. DOI: 10.1002/gcc.20515.
6. Bulgakova O, Kussainova A, Kakabayev A, Kausbekova A, Bersimbaev R. Association of polymorphism TP53 Arg72Pro with radon-induced lung cancer in the Kazakh population. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2019;23(5): 594–599. DOI: 10.18699/VJ19.530. (In Russian).
7. Yanishevskaya MA, Blinova EA, Korechenkova AV, Akleyev AV. Association between the rs1052133 polymorphism of the OGG1 gene and the risk of malignant neoplasms development in people chronically exposed to radiation. Byulleten Radiatsiya i Risk = Bulletin Radiation and Risk. 2023;32(3): 97–108. DOI: 10.21870/0131-3878-2023-32-3-97-108. (In Russian).
8. Blinova EA, Korechenkova AV, Yanishevskaya MA, Akleyev AV. Effect of Repair Gene Polymorphism on the Risk of Malignant Neoplasm Development after Chronic Radiation Exposure. Meditsinskaya Radiologiya i Radiatsionnaya Bezopasnost = Medical Radiology and Radiation Safety. 2024;69(5): 53–58. DOI: 10.33266/1024-6177-2024-69-5-53-58. (In Russian).
9. Blinova EA, Yanishevskaya MA, Korechenkova AV, Akleyev AV. Association Between Single Nucleotide Polymorphisms of Apoptosis and Cell Cycle Control Genes and the Risk of Cancer Development in Chronically Exposed Persons. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2023;63(1): 60–70. DOI: 10.31857/S0869803123010046. (In Russian).
10. Papadakis E, Soulitzis N, Spandidos D. Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes. British Journal of Cancer. 2002;87: 1013–1018. DOI: 10.1038/sj.bjc.6600595.
11. Blinova EA, Nikiforov VS, Yanishevskaya MA, Akleyev AA. Single nucleotide polymorphisms and expression of genes for immune competent cell proliferation and differentiation in radiation-exposed individuals. Vavilovskiy zhurnal genetiki i selektsii = Vavilov Journal of Genetics and Breeding. 2020;24(4): 399–406. DOI: 10.18699/VJ20.632. (In Russian).
12. Ritchie MD, Hahn LW, Moore JH. Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genetic Epidemiology. 2003;24(2): 150–157. DOI: 10.1002/gepi.10218.
13. Mbemi A, Khanna S, Njiki S, Yedjou CG, Tchounwou PB. Impact of gene-environment interactions on cancer development. International Journal of Environmental Research and Public Health. 2020;17(21): 8089. DOI: 10.3390/ijerph17218089.
14. Hutter CM, Mechanic LE, Chatterjee N, Kraft P, Gillanders EM; NCI Gene-Environment Think Tank. Gene-environment interactions in cancer epidemiology: a National Cancer Institute Think Tank report. Genetic Epidemiology. 2013;37(7): 643–657. DOI: 10.1002/gepi.21756.
15. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Human Molecular Genetics. 2014;23(R1): R89–R98. DOI: 10.1093/hmg/ddu328.
16. Sato G, Shirai Y, Namba S, Edahiro R, Sonehara K, Hata T, et al. Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis. Nature communications. 2023;14: 3671. DOI: 10.1038/s41467-023-39136-7.
Review
For citations:
Blinova E.A., Korechenkova A.V., Akleyev A.V. Contribution of the genetic polymorphisms to cancer risk in chronically exposed individuals. Radiatsionnaya Gygiena = Radiation Hygiene. 2025;18(3):7-17. (In Russ.) https://doi.org/10.21514/1998-426X-2025-18-3-7-17