Association of the epidermal growth factor gene +61A>G polymorphism with hepatocellular carcinoma in an Iranian population

Mehdi Gholizadeh, Ayyoob Khosravi, Pedram Torabian, Naghmeh Gholipoor, Nader Mansour Samaei

Abstract


43

Background: The association of epidermal growth factor (EGF) gene +61A/G polymorphism (rs4444903) and hepatocellular carcinoma (HCC) has been investigated in several populations. However, the findings are controversial. The aim of this study was to address the association of the EGF gene +61A/G polymorphisms and HCC susceptibility in an Iranian population. Materials and Methods: A total of 40 unrelated HCC patients and 106 healthy individuals were enrolled in this study. Genomic DNA of HCC patients was extracted from formalin-fixed, paraffin-embedded samples using CinnaPure DNA kit according to manufacturer’s instructions. Genomic DNA of healthy individuals, also, was extracted from peripheral blood cells using the boiling method. The rs4444903 (A/G) polymorphism was genotyped using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Results: Significant association was found for the EGF +61A allele and HCC risk [OR = 1.72, 95% CI (1.02 - 2.90), P value = 0.04]. Also, significant association was observed for the EGF +61A/G genotypes and HCC risk under codominant and dominant models by SNPStats software analysis. Conclusion: Our findings suggest that the EGF gene +61A/G polymorphism (rs4444903) might be a risk factor for susceptibility to HCC in Iranian population. Howeverfurther studies using more samples are needed.


Keywords


Epidermal growth factor, EGF +61A>G polymorphism, Hepatocellular carcinoma

References


Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011;61(2):69-90.

Yuan J-M, Fan Y, Ognjanovic S, Wang R, Van Den Berg D, Govindarajan S, et al. Genetic polymorphisms of epidermal growth factor in relation to risk of hepatocellular carcinoma: two case-control studies. BMC gastroenterology. 2013;13(1):32.

Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127(5):S5-S16.

Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM. Obesity and hepatocellular carcinoma. Gastroenterology. 2004;127(5):S97-S103.

Donato F, Boffetta P, Puoti M. A meta‐analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. International Journal of Cancer. 1998;75(3):347-54.

Mimi CY, Yuan J-M. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127(5):S72-S8.

Yuan JM, Govindarajan S, Arakawa K, Yu MC. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US. Cancer. 2004;101(5):1009-17.

Knight JC. Functional implications of genetic variation in non-coding DNA for disease susceptibility and gene regulation. Clinical Science. 2003;104(5):493-502.

Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, et al. Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nature genetics. 2011;43(5):455-8.

Limaye PB, Bowen WC, Orr AV, Luo J, Tseng GC, Michalopoulos GK. Mechanisms of hepatocyte growth factor–mediated and epidermal growth factor–mediated signaling in transdifferentiation of rat hepatocytes to biliary epithelium. Hepatology. 2008;47(5):1702-13.

FISHER DA, LAKSHMANAN J. Metabolism and Effects of Epidermal Growth Factor and Related Growth Factors in Mammals*. Endocrine Reviews. 1990;11(3):418-42.

Mullhaupt B, Feren A, Fodor E, Jones A. Liver expression of epidermal growth factor RNA. Rapid increases in immediate-early phase of liver regeneration. Journal of Biological Chemistry. 1994;269(31):19667-70.

Blanc P, Etienne H, Daujat M, Fabre I, Zindy F, Domergue J, et al. Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor alpha, and human serum. Gastroenterology. 1992;102(4 Pt 1):1340-50.

Giannelli G, Sgarra C, Porcelli L, Azzariti A, Antonaci S, Paradiso A. EGFR and VEGFR as potential target for biological therapies in HCC cells. Cancer letters. 2008;262(2):257-64.

Singletary SE, Baker FL, Spitzer G, Tucker SL, Tomasovic B, Brock WA, et al. Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer research. 1987;47(2):403-6.

de Almeida LO, Custódio AC, dos Santos MJ, Almeida JR, Clara CA, Pinto GR, et al. The A61G EGF polymorphism is associated with development of extraaxial nervous system tumors but not with overall survival. Cancer genetics and cytogenetics. 2010;198(1):15-21.

Lanuti M, Liu G, Goodwin JM, Zhai R, Fuchs BC, Asomaning K, et al. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clinical Cancer Research. 2008;14(10):3216-22.

Shahbazi M, Pravica V, Nasreen N, Fakhoury H, Fryer AA, Strange RC, et al. Association between functional polymorphism in EGF gene and malignant melanoma. The Lancet. 2002;359(9304):397-401.

Xu W, Li Y, Wang X, Chen B, Liu S, Wang Y, et al. Association between EGF promoter polymorphisms and cancer risk: a meta-analysis. Medical Oncology. 2010;27(4):1389-97.

Qi P, Wang H, Chen YM, Sun XJ, Liu Y, Gao CF. No association of EGF 5'UTR variant A61G and hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection. Pathology. 2009;41(6):555-60.

Yang Z, Wu Q, Shi Y, Nie Y, Wu K, Fan D. Epidermal growth factor 61A>G polymorphism is associated with risk of hepatocellular carcinoma: a meta-analysis. Genetic testing and molecular biomarkers. 2012;16(9):1086-91.

Zhong JH, You XM, Gong WF, Ma L, Zhang Y, Mo QG, et al. Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a meta-analysis. PloS one. 2012;7(3):e32159.

Kojiro M, Wanless IR, Alves V, Badve S, Balabaud C, Bedossa P, et al. Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology. 2009;49(2):658-64.

Scott JA, Brogdon WG, Collins FH. Identification of single specimens of the Anopheles gambiae complex by the polymerase chain reaction. The American journal of tropical medicine and hygiene. 1993;49(4):520-9.

SNPstats software. Available : http://bioinfo.iconcologia.net/snpstats/start.htm. Accessed 2016.

Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928-9.

Khosravi A, Javan B, Tabatabaiefar MA, Ebadi H, Fathi D, Shahbazi M. Association of interleukin-1 gene cluster polymorphisms and haplotypes with multiple sclerosis in an Iranian population. J Neuroimmunol. 2015;288:114-9.

Mullhaupt B, Feren A, Fodor E, Jones A. Liver expression of epidermal growth factor RNA. Rapid increases in immediate-early phase of liver regeneration. J Biol Chem. 1994;269(31):19667-70.

Stoscheck CM, King LE, Jr. Role of epidermal growth factor in carcinogenesis. Cancer Res. 1986;46(3):1030-7.

Peng Q, Li S, Qin X, Lao X, Chen Z, Zhang X, et al. EGF +61A/G polymorphism contributes to increased gastric cancer risk: evidence from a meta-analysis. Cancer Cell Int. 2014;14:134.

Li Y, Xie Q, Lu F, Zhao J, Mao P, Li Z, et al. Association between epidermal growth factor 61A/G polymorphism and hepatocellular carcinoma susceptibility in Chinese patients. Liver Int. 2010;30(1):112-8.

Shahbazi M, Pravica V, Nasreen N, Fakhoury H, Fryer AA, Strange RC, et al. Association between functional polymorphism in EGF gene and malignant melanoma. Lancet. 2002;359(9304):397-401.

Jiang G, Yu K, Shao L, Yu X, Hu C, Qian P, et al. Association between epidermal growth factor gene +61A/G polymorphism and the risk of hepatocellular carcinoma: a meta-analysis based on 16 studies. BMC Cancer. 2015;15:314.

Abu Dayyeh BK, Yang M, Fuchs BC, Karl DL, Yamada S, Sninsky JJ, et al. A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma. Gastroenterology. 2011;141(1):141-9.

Tanabe KK, Lemoine A, Finkelstein DM, Kawasaki H, Fujii T, Chung RT, et al. Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. Jama. 2008;299(1):53-60.




DOI: http://dx.doi.org/10.22037/ghfbb.v0i0.1165

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PISSN: 2008-2258

EISSN: 2008-4234


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