Genetic polymorphisms of epidermal growth factor in relation to risk of hepatocellular carcinoma: two case-control studies

BMC Gastroenterology

Mimi C Yu²  Sugantha Govindarajan¹  David Van Den Berg²  Renwei Wang⁶  Simona Ognjanovic⁴  Yunhua Fan³  Jian-Min Yuan⁵ 

[1] Department of Pathology, Rancho Los Amingo Medical Center, 7601 E. Imperial Highway, JPI Building Basement, Downey, CA, 90242, USA;The USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90089, USA;Masonic Cancer Center, University of Minnesota, 554 CCRB, 425 East River Road, Minneapolis, MN, 55455, USA;Masonic Cancer Center, University of Minnesota, 1-185 Moos Tower, 515 Delaware Street SE, Minneapolis, MN, 55455, USA;Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, A529 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA;Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, Suite 4C, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA

关键词: Hepatocellular carcinoma;    Cytokines;    T-helper;    Epidermal growth factor;   

Others  :  858173
DOI  :  10.1186/1471-230X-13-32

 received in 2012-06-27, accepted in 2013-02-05,  发布年份 2013

【 摘 要 】

Background

Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk.

Methods

The EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China.

Results

Following adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93–12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China.

Conclusion

Genetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.

【 授权许可】

   
2013 Yuan et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Ferlay J, Bray F, Pisani P, Parkin DM: GLOBOCAN 2002 Cancer Incidence, Mortality and Prevalence Worldwide, IARC CancerBase No. 5. version 20 edition. IARC Press: Lyon; 2004.
• [2]Ross RK, Yuan J-M, Yu MC, Wogan GN, Qian GS, Tu JT, Groopman JD, Gao YT, Henderson BE: Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992, 339(8799):943-946.
• [3]Yu MC, Yuan J-M: Environmental factors and risk for hepatocellular carcinoma. Gastroenterology 2004, 127(5 Suppl 1):S72-S78.
• [4]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. Int J Cancer 1998, 75(3):347-354.
• [5]Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM: Obesity and hepatocellular carcinoma. Gastroenterology 2004, 127(5 Suppl 1):S97-S103.
• [6]Yuan J-M, 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 U.S. Cancer 2004, 101(5):1009-1017.
• [7]Farazi PA, DePinho RA: Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006, 6(9):674-687.
• [8]Ognjanovic S, Hainaut P: Inflammation in carcinogenesis. In Comprehensive Toxicology. Edited by Sipes IG, McQueen CA, Gandolfi AJ. Oxford: Elsevier; 2010.
• [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):19667-19670.
• [10]Michalopoulos GK, DeFrances MC: Liver regeneration. Science 1997, 276(5309):60-66.
• [11]Singletary SE, Baker FL, Spitzer G, Tucker SL, Tomasovic B, Brock WA, Ajani JA, Kelly AM: Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer Res 1987, 47(2):403-406.
• [12]Tonjes RR, Lohler J, O’Sullivan JF, Kay GF, Schmidt GH, Dalemans W, Pavirani A, Paul D: Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice. Oncogene 1995, 10(4):765-768.
• [13]Borlak J, Meier T, Halter R, Spanel R, Spanel-Borowski K: Epidermal growth factor-induced hepatocellular carcinoma: gene expression profiles in precursor lesions, early stage and solitary tumours. Oncogene 2005, 24(11):1809-1819.
• [14]Shahbazi M, Pravica V, Nasreen N, Fakhoury H, Fryer AA, Strange RC, Hutchinson PE, Osborne JE, Lear JT, Smith AG, et al.: Association between functional polymorphism in EGF gene and malignant melanoma. Lancet 2002, 359(9304):397-401.
• [15]Tanabe KK, Lemoine A, Finkelstein DM, Kawasaki H, Fujii T, Chung RT, Lauwers GY, Kulu Y, Muzikansky A, Kuruppu D, et al.: Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA 2008, 299(1):53-60.
• [16]Costa BM, Ferreira P, Costa S, Canedo P, Oliveira P, Silva A, Pardal F, Suriano G, Machado JC, Lopes JM, et al.: Association between functional EGF + 61 polymorphism and glioma risk. Clin Cancer Res 2007, 13(9):2621-2626.
• [17]Hamai Y, Matsumura S, Matsusaki K, Kitadai Y, Yoshida K, Yamaguchi Y, Imai K, Nakachi K, Toge T, Yasui W: A single nucleotide polymorphism in the 5' untranslated region of the EGF gene is associated with occurrence and malignant progression of gastric cancer. Pathobiology 2005, 72(3):133-138.
• [18]Lanuti M, Liu G, Goodwin JM, Zhai R, Fuchs BC, Asomaning K, Su L, Nishioka NS, Tanabe KK, Christiani DC: A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res 2008, 14(10):3216-3222.
• [19]Lim YJ, Kim JW, Song JY, Hong MS, Jin SY, Yoon SH, Park HJ, Choe BK, Lee JJ, Yim SV, et al.: Epidermal growth factor gene polymorphism is different between schizophrenia and lung cancer patients in Korean population. Neurosci Lett 2005, 374(3):157-160.
• [20]Yeh FS, Yu MC, Mo CC, Luo S, Tong MJ, Henderson BE: Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. Cancer Res 1989, 49(9):2506-2509.
• [21]Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas D: Cancer Incidence in Five Continents. Lyon, France: International Agency for Research on Cancer; 2002.
• [22]Nieters A, Yuan J-M, Sun CL, Zhang ZQ, Stoehlmacher J, Govindarajan S, Yu MC: Effect of cytokine genotypes on the hepatitis B virus-hepatocellular carcinoma association. Cancer 2005, 103(4):740-748.
• [23]Ognjanovic S, Yuan J-M, Chaptman AK, Fan Y, Yu MC: Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA. Carcinogenesis 2009, 30(5):758-762.
• [24]Breslow NE, Day NE: Statistical methods in cancer research. Volume 1. The analysis of case–control studies, vol. 32. Lyon: IARC Scientific Publication; 1980.
• [25]Michalopoulos GK, DeFrances M: Liver regeneration. Adv Biochem Eng Biotechnol 2005, 93:101-134.
• [26]Muller M, Morotti A, Ponzetto C: Activation of NF-kappaB is essential for hepatocyte growth factor-mediated proliferation and tubulogenesis. Mol Cell Biol 2002, 22(4):1060-1072.
• [27]Saso K, Moehren G, Higashi K, Hoek JB: Differential inhibition of epidermal growth factor signaling pathways in rat hepatocytes by long-term ethanol treatment. Gastroenterology 1997, 112(6):2073-2088.
• [28]Waris G, Siddiqui A: Interaction between STAT-3 and HNF-3 leads to the activation of liver-specific hepatitis B virus enhancer 1 function. J Virol 2002, 76(6):2721-2729.
• [29]Yeo EJ, Lim HK, Park SC: Effect of short-term ethanol on the proliferative response of Swiss 3 T3 cells to mitogenic growth factors. Exp Mol Med 2000, 32(3):161-169.
• [30]Wolff GS, Chiang PJ, Smith SM, Romero R, Armant DR: Epidermal growth factor-like growth factors prevent apoptosis of alcohol-exposed human placental cytotrophoblast cells. Biol Reprod 2007, 77(1):53-60.
• [31]Abu Dayyeh BK, Yang M, Fuchs BC, Karl DL, Yamada S, Sninsky JJ, O’Brien TR, Dienstag JL, Tanabe KK, Chung RT: A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma. Gastroenterology 2011, 141(1):141-149.
• [32]Galmozzi E, Colombo M: Genetic testing for hepatocellular carcinoma: an ambitious goal still to achieve. J Hepatol 2012, 56(6):1415-1416.
• [33]Li TF, Ren KW, Liu PF: Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9,779 cases and 15,932 controls. DNA Cell Biol 2012, 31(4):568-574.
• [34]Zhong JH, You XM, Gong WF, Ma L, Zhang Y, Mo QG, Wu LC, Xiao J, Li LQ: Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a meta-analysis. PLoS One 2012, 7(3):e32159.