Increased Expression of CYP2E1 Gene in Gastric Cancer May be a Molecular Marker for Mazandaran Province Population

Document Type : Research Article

Authors

1 Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran

2 Department of Toxicology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Surgery, School of Medicine, Babol University of Medical Sciences, Babol, Iran

Abstract

Cytochrome P450 2E1 (CYP2E1) enzyme metabolically activates a large number of low molecular mass xenobiotics probably involved in gastric cancer incidence through activation of procarcinogens. North of Iran is amongst high incidence rate areas of gastric carcinoma where environmental carcinogenic compounds, including agricultural pesticides, are massively used. In this report, we quantitatively compared CYP2E1 gene expression between tumoral and nontumoral-marginal tissues of gastric cancer patients as well as normal healthy gastric tissues by real-time PCR. Results showed that CYP2E1 gene cDNA copy numbers were relatively increased in tumoral group vs. nontumoral-marginal and normal healthy groups. Comparison of means DDCT by Dunkan’s test statistically verified significant differences of cyp2E1 cDNA copy numbers between tumoral and healthy tissues (P=0.0018). It seems that the increased CYP2E1 gene expression may be associated with increased risk for gastric cancer. So, we recommended that CYP2E1 gene expression may be an appropriate molecular marker to determine individual sensitivity to gastric cancer and also for designing cancer prevention programs.

Keywords


Cai L, Zheng ZL, Zhang ZF. 2005. Cytochrome p450 2E1 polymorphisms and the risk of gastric cardia cancer. World J Gastroenterol 11(12): 1867-1871.
Caro AA, Cederbaum AI. 2004. Oxidative stress, toxicology, and pharmacology of CYP2E1. Annu Rev Pharmacol Toxicol 44: 27-42.
Colagar AH, Amjadi Souraki O. 2012. Review of pumpkin anticancer effects. Quran Med. 1(4): 77-88.
Coon MJ. 2005. Cytochrome P450: nature's most versatile biological catalyst. Annu Rev Pharmacol Toxicol 45: 1-25.
Danko IM, Chaschin NA. 2005. Association of CYP2E1 gene polymorphism with predisposition to cancer development. Exp Oncol 27(4): 248-256.
Gao CM, Takezaki T, Wu JZ, et al. 2007. CYP2E1 RsaI polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking. World J Gastroenterol 13(43): 5725-30.
Glatt HR. 2000. An overview of bioactivation of chemical carcinogens. Biochem Soc Trans 28(2): 1-6.
Gonzalez FJ. 2005. Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res 569(1): 101-110.
Guengerich FP. 1988. Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res 48(11): 2946-2954.
Helmig S, Dohrel J, Schneider J. 2010. Decreased CYP2E1 mRNA expression in human leucocytes in patients with fibrotic and inflammatory lung diseases. Int J Mol Med 26(1): 143-149.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. 2011. Global cancer statistics. CA Cancer J Clin 61(2): 69-90.
Kamalipour S, Barzegar A, Nikbakhsh N, Shokrzadeh M. 2016. Study of CYP2E1 gene RsaI/PstI polymorphisms in patients with gastric cancer in north of Iran. Res Mol Med 4(4): 22-27.
Khalatbari K, Sadat Shandiz A, Salehzadeh A, Ahmadzadeh M. 2017. Evaluation of cytotoxicity activity and NM23 gene expression in T47D breast cancer cell line treated with glycyrrhiza glabra extract. J Genet Resour 3(1): 47-53
Kim I, Xu W, Reed JC. 2008. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov 7(12): 1013-1030.
Lao-Sirieix P, Caldas C, Fitzgerald RC. 2010. Genetic predisposition to gastro-oesophageal cancer. Curr Opin Genet Dev 20(3): 210-217.
Leung T, Rajendran R, Singh S, Garva R, Krstic-Demonacos M, Demonacos C. 2013. Cytochrome P450 2E1 (CYP2E1) regulates the response to oxidative stress and migration of breast cancer cells. Breast Cancer Res 15(6): R107.
Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25 (4): 402-408.
Malekzadeh R, Derakhshan MH, Malekzadeh Z. 2009. Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med 12(6): 576-583
Mohebbi M, Mahmoodi M, Wolfe R, Nourijelyani K, Mohammad K, Zeraati H, Fotouhi A. 2008. Geographical spread of gastrointestinal tract cancer incidence in the Caspian Sea region of Iran: spatial analysis of cancer registry data. BMC Cancer 8(1): 137.
Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. 2008. Cancer incidence and mortality in Iran. Ann Oncol 20(3): 556-563.
Nair PC, McKinnon RA, Miners JO. 2016. Cytochrome P450 structure-function: insights from molecular dynamics simulations. Drug Metab Rev 48(3): 434-452.
Nebert DW, Dalton TP. 2006. The role of cytochrome P450 enzymes in endogenous signaling pathways and environmental carcinogenesis. Nat Rev Cancer 6(12): 947-960.
Oyama T, Sugio K, Uramoto H, Kawamoto T, Kagawa N, Nadaf S, Carbone D, Yasumoto K. 2007. Cytochrome P450 expression (CYP) in non-small cell lung cancer. Front Biosci 12: 2299-2308.
Rutkowski DT, Kaufman RJ. 2004. A trip to the ER: coping with stress. Trends Cell Biol 14(1): 20-28.
Sambrook J, Fritsh E, Maniatis T. 1989. Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press. Cold Spring Harbor. Second edition.
Shahriary GM, Galehdari H, Jalali A, Zanganeh F, Alavi SMR, Aghanoori MR. CYP2E1*5B, CYP2E1*6, CYP2E1*7B, CYP2E1*2, and CYP2E1*3 allele frequencies in Iranian populations. Asian Pac J Cancer Prev 13(12): 6505-6510.
Shikata K, Doi Y, Yonemoto K, Arima H, Ninomiya T, Kubo M, Tanizaki Y, Matsumoto T, Iida M, Kiyohara Y. 2008. Population-based prospective study of the combined influence of cigarette smoking and Helicobacter pylori infection on gastric cancer incidence: the Hisayama Study. Am J Epidemiol 168(12): 1409-1415.
Shokrzadeh M, Karami M, Ebrahimi Ghadi MA. 2013. Measuring organophosphorus insecticide residue in rice produced in Amol, North of Iran. J Mazandaran Univ Med Sci 23(1): 215-221.
Siegel RL, Miller KD, Jemal A. 2016. Cancer statistics. CA Cancer J Clin 66(1): 7-30.
Tang K, Li X, Xing Q, Li W, Feng G, He L, Qin S. 2010. Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in Chinese Han populations from four different geographic areas of Mainland China. Genomics 95(4): 224-229.
Vaclavikova R, Hubackova M, Stribrna-Sarmanova J, Kodet R, Mrhalova M, Novotny JAN, Gut I, Soucek P. 2007. RNA expression of cytochrome P450 in breast cancer patients. Anticancer Res 27(6C): 4443-4450.
Yuan JS, Reed A, Chen F, Stewart CN. 2006. Statistical analysis of real-time PCR data. BMC Bioinformatics 7: 85.