ORIGINAL RESEARCH

Methylation of cell cycle and apoptosis genes’ promoters in exposed individuals with subsequent malignant neoplasms

About authors

1 Urals Research Center for Radiation Medicine, Chelyabinsk, Russia

2 Chelyabinsk State University, Chelyabinsk, Russia

Correspondence should be addressed: Eugenia A. Blinova
Vorovskogo, 68A, Chelyabinsk, 454141, Russia; ur.mrcru@avonilb

About paper

Acknowledgements: the article was prepared in the context of the Federal Target Program "Modernization of high-tech methods of identification of medical consequences of exposure to radiation of personnel of the Mayak Production Association and population of the Ural region," Contract № 27.501.21.2 of 11.06.2021.

Author contributions: E.A. Blinova — study planning, generalization of primary material, analysis and discussion of the results, article drafting; A.V. Korechenkova — laboratory tests, article drafting; V.S. Nikiforov — laboratory tests, article drafting; A.V. Akleyev — study planning, article editing, authoring of the final version of the article.

Compliance with ethical standards: the study was approved by the Ethics Committee of the Urals Research Center for Radiation Medicine of the FMBA of Russia (Minutes #2 of July 20, 2021). All participants signed the informed consent form to participate in the study.

Received: 2023-10-03 Accepted: 2023-11-13 Published online: 2023-12-25
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  1. Smith P, McGuffog L, Easton DF, Mann GJ, Pupo GM, Newman B, et al. A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer. 2006; 45 (7): 646–55. DOI: 10.1002/gcc.20330.
  2. Barnoud T, Parris JLD, Murphy ME. Common genetic variants in the TP53 pathway and their impact on cancer. J Mol Cell Biol. 2019; 11 (7): 578–85. DOI: 10.1093/jmcb/mjz052.
  3. Hall MJ, Bernhisel R, Hughes E, Larson K, Rosenthal ET, Singh NA, et al. Germline Pathogenic Variants in the Ataxia Telangiectasia Mutated (ATM) Gene are Associated with High and Moderate Risks for Multiple Cancers. Cancer Prev Res (Phila). 2021; 14 (4): 433–40. DOI: 10.1158/1940-6207.CAPR-20-0448.
  4. Verma M, Rogers S, Divi RL, Schully SD, Nelson S, Joseph Su, et al. Epigenetic research in cancer epidemiology: trends, opportunities, and challenges. Cancer Epidemiol Biomarkers Prev. 2014; 23 (2): 223–33. DOI: 10.1158/1055-9965.EPI-130573.
  5. Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Research. 2001; 61 (8): 3225–9. PubMed PMID: 11309270.
  6. Belinsky SA. Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev Cancer. 2004; 4 (9): 707–17. DOI: 10.1038/nrc1432.
  7. Park JY. Promoter hypermethylation in prostate cancer. Cancer Control. 2010; 17(4): 245–55. DOI: 10.1177/107327481001700405.
  8. Suzuki K, Suzuki I, Leodolter A, Alonso S, Horiuchi S, Yamashita K, et al. Global DNA demethylation in gastrointestinal cancer is age dependent and precedes genomic damage. Cancer Cell. 2006; 9(3): 199–207. DOI: 10.1016/j.ccr.2006.02.016.
  9. Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009; 1 (2): 239–59. DOI: 10.2217/epi.09.33
  10. Wild CP, Scalbert A, Herceg Z. Measuring the exposome: a powerful basis for evaluating environmental exposures and cancer risk. Environ Mol Mutagen. 2013; 54 (7): 480–99. DOI: 10.1002/em.21777.
  11. Relton CL, Davey SG. Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment. PLoS Med. 2010; 7 (10): e1000356. DOI: 10.1371/journal.pmed.1000356.
  12. Suter CM, Martin DI, Ward RL. Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet. 2004; 36 (5): 497– 501. DOI: 10.1038/ng1342.
  13. Zheng Y, Joyce BT, Colicino E, Liu L, Zhang W, Dai Q, et al. Blood epigenetic age may predict cancer incidence and mortality. EBioMedicine. 2016; 5: 68–73. DOI: 10.1016/j. ebiom.2016.02.008.
  14. Durso DF, Bacalini MG, Sala C, Pirazzini C, Marasco E, Bonafé M, et al. Acceleration of leukocytes' epigenetic age as an early tumor and sex-specific marker of breast and colorectal cancer. Oncotarget. 2017; 8 (14): 23237–45. DOI: 10.18632/oncotarget.15573.
  15. Kresovich JK, Xu Z, O'Brien KM, Weinberg CR, Sandler DP, Taylor JA. Methylation-based biological age and breast cancer risk. J Natl Cancer Inst. 2019; 111 (10): 1051–8. DOI: 10.1093/jnci/djz020.
  16. Dugué PA, Bassett JK, Wong EM, Joo JE, Li S, Yu C. Biological aging measures based on blood DNA methylation and risk of cancer: a prospective study. JNCI Cancer Spectr. 2020; 5 (1): pkaa109. DOI: 10.1093/jncics/pkaa109.
  17. Wang C, Ni W, Yao Y, Just A, Heiss J, Wei Y. DNA methylationbased biomarkers of age acceleration and all-cause death, myocardial infarction, stroke, and cancer in two cohorts: The NAS, and KORA F4. EBioMedicine. 2021; 63: 103151. DOI: 10.1016/j.ebiom.2020.103151.
  18. Li X, Schöttker B, Holleczek B, Brenner H. Associations of DNA methylation algorithms of aging and cancer risk: Results from a prospective cohort study. EBioMedicine. 2022; 81: 104083. DOI: 10.1016/j.ebiom.2022.104083.
  19. Ennour-Idrissi K, Dragic D, Durocher F, Diorio C. Epigenome-wide DNA methylation and risk of breast cancer: a systematic review. BMC Cancer. 2020; 20 (1): 1048. DOI: 10.1186/s12885-020-07543-4.
  20. Degteva MO, Napier BA, Tolstykh EI, Shishkina EA, Bougrov NG, Krestinina LYu, et al. Individual dose distribution in cohort of people exposed as a result of radioactive contamination of the Techa River. Medical Radiology and Radiation Safety. 2019; 64 (3): 46–53. Russian.
  21. Nikiforov VS. Soderzhanie matrichnoy RNK genov, vovlechennykh v kletochnyy gomeostaz cheloveka, v otdalennye sroki posle khronicheskogo oblucheniya [dissertation]. Obninsk; 2021. Russian.
  22. Blinova EA, Nikiforov VS, Kotikova AI, Yanishevskaya MA, Akleyev AV. Methylation Status of Apoptosis Genes and Intensity of Apoptotic Death of Peripheral Blood Lymphocytes in Persons Chronically Exposed to Radiation. Mol Biol (Mosk). 2022; 56 (6): 1072–82. DOI 10.1134/S002689332205003X.
  23. Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993; 74 (4): 609–19. DOI: 10.1016/0092-8674(93)90509-o.
  24. Gopisetty G, Ramachandran K, Singal R. DNA methylation and apoptosis. Mol Immunol. 2006; 43 (11): 1729–40. DOI: 10.1016/j. molimm.2005.11.010.
  25. Alipour M, Zargar SJ, Safarian S, Fouladdel S, Azizi E, Jafargholizadeh N. The study of DNA methylation of BAX gene promoter in breast and colorectal carcinoma cell lines. Iran J Cancer Prev. 2013; 6 (2): 59–64.
  26. Blinova EA, Kotikova AI, Akleev AV. The intensity of blood lymphocytes apoptosis in exposed individuals with obligate forms of precancerous conditions. Bulletin of Experimental Biology and Medicine. 2023; 176 (8): 233–6. Russian.
  27. Verma M, Rogers S, Divi RL, Schully SD, Nelson S, Joseph Su L, et al. Epigenetic research in cancer epidemiology: trends, opportunities, and challenges. Cancer Epidemiol Biomarkers Prev. 2014; 23 (2): 223–33. DOI: 10.1158/1055-9965.EPI-13-0573.
  28. Flanagan JM, Munoz-Alegre M, Henderson S, Tang T, Sun P, Johnson N, et al. Gene-body hypermethylation of ATM in peripheral blood DNA of bilateral breast cancer patients. Hum Mol Genet. 2009; 18 (7): 1332–42. DOI: 10.1093/hmg/ddp033.