ABSTRACT:
Background: The hepatic cytochrome P450 2E1 (CYP2E1) enzyme plays an important role in the metabolic activation of nitrosamines and other carcinogenic compounds. Aim of the study: To determine the effect of chemotherapy and radiation for colorectal cancer patients on some biochemical and molecular parameters. Patients and methods: The current study was conducted in the Department of Biology at the College of Science at the University of Al-Qadisiyah and in cooperation with the Cancer Center in the Najaf city and the Department of Medicine City in Baghdad, Iraq during the period from November 15, 2019, to May 6, 2020. The study group included a total of (90) samples were taken from males and females of ages ranged between (33 years to 80 years) and then it was divided into two groups. The first included (60) samples of people with colorectal cancer (CRC), and the second included (30) samples of people The healthy ones represented the control group. (5ml) of venous blood was withdrawn and the sample was divided into two groups, the first was placed in tubes containing an anti-clotting substance for molecular examination and kept at a temperature (-20) until use, and the other part was placed in Gel tube tubes and then placed in a centrifuge to separate Serum, for the purpose of biochemical examinations. With regard to the results of the values of oxidative stress indicators (SOD, GSH, MDA). Results: there was a significant difference in the level of (SOD, GSH) between the control and treatment groups, where the highest percentage was in the control group, followed by the radiotherapy group and then chemotherapy. The results showed a significant increase in the MDA value of the chemotherapy group compared with the radiotherapy and control group. The results of the molecular study to study the genotypes of the CYPIE2 gene showed that the C1/C1 type is the normal type for the CYPIE2 gene and that the ratio of this type did not show any significant difference between the groups, while the C2/C2 type showed no significant difference between the groups and the C2/C2 type. Conclusion: It can be concluded that the use of radiotherapy and chemotherapy to treat patients with CRC cancer has a clear effect on health and on many of the patient's physiological and biochemical indicators, and this, in turn, is reflected in the patient's ability to fight the disease.
Cite this article:
Bashar Abd Alkadhim Naji, Wijdan Thamir Mahdi. CYP2E1 Polymorphisms and Colorectal Cancer. Research Journal of Pharmacy and Technology. 2021; 14(7):3879-2. doi: 10.52711/0974-360X.2021.00673
Cite(Electronic):
Bashar Abd Alkadhim Naji, Wijdan Thamir Mahdi. CYP2E1 Polymorphisms and Colorectal Cancer. Research Journal of Pharmacy and Technology. 2021; 14(7):3879-2. doi: 10.52711/0974-360X.2021.00673 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-7-70
REFERENCES:
1. Le Marchand, L., Donlon, T., Seifried, A., and Wilkens, L. R. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiology and Prevention Biomarkers. 2002; 11(10), 1019-1024.
2. Ghagane, S., Nerli, R. B., Kaliwal, B. B., and Hiremath, M. B. Single Nucleotide Polymorphisms: A New Paradigm in Predicting the Risk of Prostate Cancer. Cell Dev Biol.2016; 5(168), 2.
3. Hu, Y., Oscarson, M., Johansson, I., Yue, Q. Y., Dahl, M. L., Tabone, M., and Ingelman-Sundberg, M. Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Molecular Pharmacology. 1997; 51(3), 370-376.
4. Wang, H. J., Ruan, H. J., He, X. J., Ma, Y. Y., Jiang, X. T., Xia, Y. J. and Tao, H. Q. MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. European Journal of Cancer.2020; 46(12), 2295-2303.
5. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., and Arcoraci, V. Oxidative Stress: Harms and Benefits for Human Health. Oxidative Medicine and Cellular Longevity.2017; 2017, 8416763.
6. Perše, M. Oxidative stress in the pathogenesis of colorectal cancer: cause or consequence?. BioMed Research International. 2013.
7. Dalle-Donne, I., Rossi, R., Colombo, R., Giustarini, D., and Milzani, A. Biomarkers of oxidative damage in human disease. Clinical Chemistry.2006; 52(4), 601-623.
8. Lobo, V., Patil, A., Phatak, A., and Chandra, N. Free radicals, antioxidants, and functional foods: Impact on Human health. Pharmacognosy Reviews. 2010; 4(8), 118.
9. Pham-Huy, L. A., He, H., and Pham-Huy, C. Free radicals, antioxidants in disease and health. International Journal of Biomedical Science: IJBS.2008; 4(2), 89.
10. Willcox, J. K., Ash, S. L., and Catignani, G. L. Antioxidants and prevention of chronic disease. Critical reviews in Food Science and Nutrition. 2004; 44(4), 275-295.
11. Misra, H. P., and Fridovich, I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological Chemistry.1972; 247(10), 3170-3175.
12. Green, M. J., and Hill, H. A. O. Chemistry of dioxygen. Methods in enzymology. 1984; (Vol. 105, pp. 3-22). Academic Press.
13. Schemedes, A., and Holmer, G. A new TBA method for determining free MDA and hydroperoxides selectively as a measure of lipid peroxidation. JAOCS. 1987; 66, 813-7.
14. Morita, M., Le Marchand, L., Kono, S., Yin, G., Toyomura, K., Nagano, J., and Maehara, Y. Genetic polymorphisms of CYP2E1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study. Cancer Epidemiology and Prevention Biomarkers.2009; 18(1), 235-241.
15. Kim, W., Lee, S., Seo, D., Kim, D., Kim, K., Kim, E., Kang, J., Seong, K. M., Youn, H., and Youn, B. Cellular Stress Responses in Radiotherapy. Cells.2019; 8(9), 1105.
16. Zhang, J., Lei, W., Chen, X., Wang, S., and Qian, W. Oxidative stress response induced by chemotherapy in leukemia treatment. Molecular and Clinical Oncology. 2018; 8(3), 391–399.
17. Sameer, A. S., Nissar, S., Qadri, Q., Alam, S., Baba, S. M., and Siddiqi, M. A. Role of CYP2E1 genotypes in susceptibility to colorectal cancer in the Kashmiri population. Human Genomics. 2011; 5(6), 530–537.
18. Lu, X. M., Zhang, Y. M., Lin, R. Y., Arzi, G., Wang, X., Zhang, Y. L., Zhang, Y., Wang, Y., and Wen, H. Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in Xinjiang, China. World Journal of Gastroenterology. 2005; 11(24), 3651–3654.
19. Cai, L., Yu, S. Z., and Zhan, Z. F. Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle, Fujian Province. World Journal of Gastroenterology. 2001; 7(6), 792–795.