DOI: https://doi.org/10.22263/2312-4156.2022.6.38
A.E. Kuzniatsou1, V.M. Tsyrkunov2
Associations of genetic variants of genes and viral DNA/RNA in liver and colon cancer
1Institute of Biochemistry of Biologically Active Compounds National Academy of Sciences of Belarus, Grodno, Republic of Belarus
2Grodno State Medical University, Grodno, Republic of Belarus
Vestnik VGMU. 2022;21(6):38-46.
Abstract.
Objectives. To establish the associations of genetic variants of genes and viral DNA/RNA in liver cancer (LC) and colorectal cancer (CRC).
Material and methods. Tissue and blood samples of individuals with morphologically diagnosed CRC and LC (n=130) served as the material for the study. The age of the examined persons was 61.8±13.7 years. A molecular biological study of the detection of DNA/RNA of the virus genome and a study of the BRCA1/2 and hMSH2 genes were performed. The control group was represented by blood samples of 80 healthy individuals with no neoplasms and infections. Statistical processing – SPSS software package.
Results. The number of mutations in the BRCA1/2 and hMSH2 genes in blood samples from patients with CRC was 2.04%, while the frequency of changes in the hMSH2 gene was 4.17%, which is lower than that of detected mutations in the same genes in tumor tissue samples (p=0.003). The frequency of mutations in the BRCA1 and hMSH2 genes in the population was 1.25%. Mutations of the BRCA 1/2 genes in women showed their dependence on the hMSH2 gene (p<0.05) in CRC. The number of mutations in LC made up 6.13% for tissue samples and 0.85% for the blood (p=0.004). The share of viral DNA/RNA carriage in LC was 9.1%, in CRC it made up 6.6%.
Conclusions. Mutations in the BRCA1/2 and hMSH2 genes in individuals with CRC in the blood and tissue samples enable us to suggest a hereditary nature of the tumor. The presence of mutations in the BRCA 1/2 genes in women should be considered as a risk factor of developing CRC: the occurrence in LC correlates with changes in exons 6 and 12 of the hMSH2 gene. The presence of mutations in the hMSH2 gene (exon 6, 12) in LC in the group of patients aged 61.4±3.4 years and 61.7±3.07 years should be considered as a risk factor of developing LC. Associations of gene mutations with viruses allow us to conclude that HPV, CMV, HSV 1/2, HHV6, HBV and HCV have a high oncogenic potential.
Keywords: liver cancer, colon cancer, viruses, mutations.
References
1. Okeanov AE, Moiseev PI, Levin LF, Evmenenko AA, Ipatiy TB; Polyakov SL, red. Cancer in Belarus: figures and facts. Analysis of data from the Belarusian Cancer Registry for 2010-2019. Minsk, RB: RNPTsOMR im NN Aleksandrova; 2020. 298 р. (In Russ.)
2. International Agency for Research of Cancer. Cancer Today. Available from: https://gco.iarc.fr/today/online-analysis-map?v=2020. [Accessed 08th December 2022].
3. Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer. 2020 Jan;1873(1):188314. doi: http://dx.doi.org/10.1016/j.bbcan.2019.188314
4. Blair VR. Familial Gastric Cancer: Genetics, Diagnosis and Management. Surg Oncol Clin N Am. 2012 Jan;21(1):35-56. doi: http://dx.doi.org/10.1016/j.soc.2011.09.003
5. Capelle LG, Van Grieken NCT, Lingsma HF, Steyerberg EW, Klokman WJ, Bruno MJ, et al. Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands. Gastroenterology. 2010 Feb;138(2):487-92. doi: http://dx.doi.org/10.1053/j.gastro.2009.10.051
6. Varley JM, McGown G, Thorncroft M, Tricker KJ, Teare MD, Santibanez-Koref MF, et al. An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53. J Med Genet. 1995 Dec;32(12):942-5. doi: http://dx.doi.org/10.1136/jmg.32.12.942
7. Van Lier MGF, Westerman AM, Wagner A, Looman CWN, Wilson JHP, de Rooij FWM, et al. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut. 2011 Feb;60(2):141-7. doi: http://dx.doi.org/10.1136/gut.2010.223750
8. Ulvik RJ. The liver in haemochromatosis. Trace Elem Med Biol. 2015;31:219-24. doi: http://dx.doi.org/10.1016/j.jtemb.2014.08.005
9. Kamihara J, Rana HQ, Garber JE. Germline TP53 mutations and the changing landscape of Li-Fraumeni syndrome. Hum Mutat. 2014 Jun;35(6):654-62. doi: http://dx.doi.org/10.1002/humu.22559
10. Talbot IC, Ritchie S, Leighton M, Hughes AO, Bussey HJ, Morson BC. Invasion of veins by carcinoma of rectum: method of detection, histological features and significance. Histopathology. 1981 Mar;5(2):141-63. doi: http://dx.doi.org/10.1111/j.1365-2559.1981.tb01774.x
11. Kuznetsov OE, Gorchakova OV. Method and kit for determination of mutations in the hMSH2 gene in a sample of human biological material: zayavka Resp Belarus': MPK G 01 N 33/48. № a20210332; zayavl 29.11.21, Afіts byul. (In Russ.)
12. Gorchakova OV, Kuznetsov OE. A method for detecting mutations in the hMLH1 gene in intestinal tumors. Med Novosti. 2019;(2):76-9. (In Russ.)
Information about authors:
A.E. Kuzniatsou – Candidate of Biological Sciences, associate professor, director of the Institute of Biochemistry of Biologically Active Compounds of the National Academy of Sciences of Belarus, https://orcid.org/0000-0002-1348-8688
E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Aleh E. Kuzniatsou;
V.M. Tsyrkunov – Doctor of Medical Sciences, professor of the Chair of Infectious Diseases, Grodno State Medical University, https://orcid.org/0000-0002-9366-6789
