Skip to main content

Advertisement

SpringerLink
Log in

Association Between Epidermal Growth Factor Polymorphism and Esophageal Squamous Cell Carcinoma Susceptibility

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Genetic factors are known to be important in the development of esophageal squamous cell carcinoma (ESCC). Epidermal growth factor (EGF) can activate several signaling pathways leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. Interindividual variations in EGF production were genetically contributed to EGF +61 G/A polymorphism. The purpose of this study is to investigate the potential association between EGF gene polymorphism and ESCC in a Chinese population. In this study, we analyzed single nucleotide polymorphism of EGF +61 G/A in 158 patients with ESCC and 212 age- and sex-matched controls in a Chinese population using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) strategy and DNA sequencing. The variant genotypes of GA/AA were associated with a significantly decreased risk of ESCC compared with the wild-type homozygote GG (OR = 0.657, 95% CI: 0.434–0.996). However, no significant difference was observed between the EGF +61 G/A polymorphism and the risk of ESCC when the analyses were stratified in terms of age, gender, smoking status, different clinical stage, and lymph node status. The EGF +61 G/A polymorphism is associated with ESCC in a Chinese population. Our data suggests that the EGF gene may play a role in the development of ESCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zou XN, Taylor PR, Mark SD, et al. Seasonal variation of food consumption and selected nutrient intake in Linxian, a high-risk area for esophageal cancer in China. Int J Vitam Nutr Res. 2002;72:375–382. doi:10.1024/0300-9831.72.6.375.

    Article  CAS  PubMed  Google Scholar 

  2. Liu JF, Wang QZ, Hou J. Surgical treatment for cancer of the oesophagus and gastric cardia in Hebei, China. Br J Surg. 2004;91:90–98. doi:10.1002/bjs.4402.

    Article  CAS  PubMed  Google Scholar 

  3. Launoy G, Milan CH, Faivre J, Pienkowski P, Milan CI, Gignoux M. Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption, mean intake and current and former consumption. Br J Cancer. 1997;75:1389–1396.

    CAS  PubMed  Google Scholar 

  4. Yokokawa Y, Ohta S, Hou J, et al. Ecological study on the risks of esophageal cancer in Ci-Xian, China: the importance of nutritional status and the use of well water. Int J Cancer. 1999;83:620–624. doi:10.1002/(SICI)1097-0215(19991126)83:5<620::AID-IJC9>3.0.CO;2-W.

    Article  CAS  PubMed  Google Scholar 

  5. Yang CS. Vitamin nutrition and gastroesophageal cancer. J Nutr. 2000;130:338S–339S.

    CAS  PubMed  Google Scholar 

  6. Matsha T, Erasmus R, Kafuko AB, Mugwanya D, Stepien A, Parker MI. Human papillomavirus associated with oesophageal cancer. J Clin Pathol. 2002;55:587–590. doi:10.1136/jcp.55.8.587.

    Article  CAS  PubMed  Google Scholar 

  7. Lavergne D, de Villiers EM. Papillomavirus in esophageal papillomas and carcinomas. Int J Cancer. 1999;80:681–684. doi:10.1002/(SICI)1097-0215(19990301)80:5<681::AID-IJC8>;3.0.CO;2-A.

    Article  CAS  PubMed  Google Scholar 

  8. Normanno N, Bianco C, De Luca A, Salomon DS. The role of EGF-related peptides in tumor growth. Front Biosci. 2001;6:D685–D707. doi:10.2741/Normano.

    Article  CAS  PubMed  Google Scholar 

  9. Fisher DA, Lakshmanan J. Metabolism and effects of epidermal growth factor and related growth factors in mammals. Endocr Rev. 1990;11:418–442.

    Article  CAS  PubMed  Google Scholar 

  10. Groenen LC, Nice EC, Burgess AW. Structure-function relationships for the EGF/TGF-alpha family of mitogens. Growth Factors. 1994;11:235–257. doi:10.3109/08977199409010997.

    Article  CAS  PubMed  Google Scholar 

  11. Wang LS, Chow KC, Chi KH, et al. Prognosis of esophageal squamous cell carcinoma: analysis of clinicopathological and biological factors. Am J Gastroenterol. 1999;94:1933–1940. doi:10.1111/j.1572-0241.1999.01233.x.

    Article  CAS  PubMed  Google Scholar 

  12. Shimada Y, Imamura M, Watanabe G, et al. Prognostic factors of oesophageal squamous cell carcinoma from the perspective of molecular biology. Br J Cancer. 1999;80:1281–1288. doi:10.1038/sj.bjc.6690499.

    Article  CAS  PubMed  Google Scholar 

  13. Kitagawa Y, Ueda M, Ando N, Ozawa S, Shimizu N, Kitajima M. Further evidence for prognostic significance of epidermal growth factor receptor gene amplification in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 1996;2:909–914.

    CAS  PubMed  Google Scholar 

  14. Iihara K, Shiozaki H, Tahara H, et al. Prognostic significance of transforming growth factor-alpha in human esophageal carcinoma. Implication for the autocrine proliferation. Cancer. 1993;71:2902–2909. doi:10.1002/1097-0142(19930515)71:10<2902::AID-CNCR2820711004>3.0.CO;2-J.

    Article  CAS  PubMed  Google Scholar 

  15. Ozawa S, Ueda M, Ando N, Abe O, Shimizu N. High incidence of EGF receptor hyperproduction in esophageal squamous-cell carcinomas. Int J Cancer. 1987;39:333–337. doi:10.1002/ijc.2910390311.

    Article  CAS  PubMed  Google Scholar 

  16. Hara F, Aoe M, Doihara H, et al. Antitumor effect of Gefitinib (‘Iressa’) on esophageal squamous cell carcinoma cell lines in vitro and in vivo. Cancer Lett. 2005;226:37–47. doi:10.1016/j.canlet.2004.12.025.

    Article  CAS  PubMed  Google Scholar 

  17. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, ‘Iressa’), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of trail in human esophageal squamous cell carcinoma. FEBS Lett. 2005;579:4069–4075. doi:10.1016/j.febslet.2005.06.031.

    Article  CAS  PubMed  Google Scholar 

  18. Shahbazi M, Pravica V, Nasreen N, et al. Association between functional polymorphism in EGF gene and malignant melanoma. Lancet. 2002;359:397–401. doi:10.1016/S0140-6736(02)07600-6.

    Article  CAS  PubMed  Google Scholar 

  19. McCarron SL, Bateman AC, Theaker JM, Howell WM. EGF +61 gene polymorphism and susceptibility to and prognostic markers in cutaneous malignant melanoma. Int J Cancer. 2003;107:673–675. doi:10.1002/ijc.11448.

    Article  CAS  PubMed  Google Scholar 

  20. Okamoto I, Roka F, Krogler J, et al. The EGF A61 G polymorphism is associated with disease-free period and survival in malignant melanoma. J Invest Dermatol. 2006;126:2242–2246. doi:10.1038/sj.jid.5700377.

    Article  CAS  PubMed  Google Scholar 

  21. Hamai Y, Matsumura S, Matsusaki K, et al. 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;72:133–138. doi:10.1159/000084116.

    Article  CAS  PubMed  Google Scholar 

  22. Jin G, Miao R, Deng Y, et al. Variant genotypes and haplotypes of the epidermal growth factor gene promoter are associated with a decreased risk of gastric cancer in a high-risk Chinese population. Cancer Sci. 2007;98:864–868. doi:10.1111/j.1349-7006.2007.00463.x.

    Article  CAS  PubMed  Google Scholar 

  23. Kang S, Kim JW, Park NH, et al. Epidermal growth factor 61 A/G polymorphism and uterine cervical cancer. Int J Gynecol Cancer. 2007;17:492–496. doi:10.1111/j.1525-1438.2007.00870.x.

    Article  CAS  PubMed  Google Scholar 

  24. Lim YJ, Kim JW, Song JY, et al. Epidermal growth factor gene polymorphism is different between schizophrenia and lung cancer patients in Korean population. Neurosci Lett. 2005;374:157–160. doi:10.1016/j.neulet.2004.10.055.

    Article  CAS  PubMed  Google Scholar 

  25. Bhowmick DA, Zhuang Z, Wait SD, Weil RJ. A functional polymorphism in the EGF gene is found with increased frequency in glioblastoma multiforme patients and is associated with more aggressive disease. Cancer Res. 2004;64:1220–1223. doi:10.1158/0008-5472.CAN-03-3137.

    Article  CAS  PubMed  Google Scholar 

  26. Costa BM, Ferreira P, Costa S, et al. Association between functional EGF +61 polymorphism and glioma risk. Clin Cancer Res. 2007;13:2621–2626. doi:10.1158/1078-0432.CCR-06-2606.

    Article  CAS  PubMed  Google Scholar 

  27. Tanabe KK, Lemoine A, Finkelstein DM, et al. Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA. 2008;299:53–60. doi:10.1001/jama.2007.65.

    Article  CAS  PubMed  Google Scholar 

  28. Spindler KL, Nielsen JN, Ornskov D, Brandslund I, Jakobsen A. Epidermal growth factor (EGF) A61 G polymorphism and EGF gene expression in normal colon tissue from patients with colorectal cancer. Acta Oncol. 2007;46:1113–1117. doi:10.1080/02841860701338853.

    Article  CAS  PubMed  Google Scholar 

  29. Teixeira AL, Ribeiro R, Cardoso D, et al. Genetic polymorphism in EGF is associated with prostate cancer aggressiveness and progression-free interval in androgen blockade-treated patients. Clin Cancer Res. 2008;14:3367–3371. doi:10.1158/1078-0432.CCR-07-5119.

    Article  CAS  PubMed  Google Scholar 

  30. Lanuti M, Liu G, Goodwin JM, et al. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res. 2008;14:3216–3222. doi:10.1158/1078-0432.CCR-07-4932.

    Article  CAS  PubMed  Google Scholar 

  31. Jain M, Kumar S, Upadhyay R, et al. Influence of apoptosis (BCL2, FAS), cell cycle (CCND1) and growth factor (EGF, EGFr) genetic polymorphisms on survival outcome: an exploratory study in squamous cell esophageal cancer. Cancer Biol Ther. 2007;6:1553–1558.

    Article  CAS  PubMed  Google Scholar 

  32. Gao LB, Wei YS, Zhou B, et al. No association between epidermal growth factor and epidermal growth factor receptor polymorphisms and nasopharyngeal carcinoma. Cancer Genet Cytogenet. 2008;185:69–73. doi:10.1016/j.cancergencyto.2008.04.019.

    Article  CAS  PubMed  Google Scholar 

  33. Inagaki M, Yoshida S, Kennedy S, Takemura N, Deguchi M, Ohara N, Maruo T. Association study between epidermal growth factor receptor and epidermal growth factor polymorphisms and endometriosis in a Japanese population. Gynecol Endocrinol. 2007;23:474–478.

    Google Scholar 

  34. Anttila S, Illi A, Kampman O, Mattila KM, Lehtimaki T, Leinonen E. Association of EGF polymorphism with schizophrenia in Finnish men. NeuroReport. 2004;15:1215–1218. doi:10.1097/00001756-200405190-00027.

    Article  CAS  PubMed  Google Scholar 

  35. Vauleon E, Auger N, Benouaich-Amiel A, et al. The 61 A/G EGF polymorphism is functional but is neither a prognostic marker nor a risk factor for glioblastoma. Cancer Genet Cytogenet. 2007;172:33–37. doi:10.1016/j.cancergencyto.2006.07.013.

    Article  CAS  PubMed  Google Scholar 

  36. James MR, Hayward NK, Dumenil T, Montgomery GW, Martin NG, Duffy DL. Epidermal growth factor gene (EGF) polymorphism and risk of melanocytic neoplasia. J Invest Dermatol. 2004;123:760–762. doi:10.1111/j.0022-202X.2004.23305.x.

    Article  CAS  PubMed  Google Scholar 

  37. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19:183–232. doi:10.1016/1040-8428(94)00144-I.

    Article  CAS  PubMed  Google Scholar 

  38. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res. 2003;284:31–53. doi:10.1016/S0014-4827(02)00098-8.

    Article  CAS  PubMed  Google Scholar 

  39. Stoscheck CM, King LE Jr. Role of epidermal growth factor in carcinogenesis. Cancer Res. 1986;46:1030–1037.

    CAS  PubMed  Google Scholar 

  40. Singletary SE, Baker FL, Spitzer G, et al. Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer Res. 1987;47:403–406.

    CAS  PubMed  Google Scholar 

  41. Amend KL, Elder JT, Tomsho LP, et al. EGF gene polymorphism and the risk of incident primary melanoma. Cancer Res. 2004;64:2668–2672. doi:10.1158/0008-5472.CAN-03-3855.

    Article  CAS  PubMed  Google Scholar 

  42. Randerson-Moor JA, Gaut R, Turner F, et al. The relationship between the epidermal growth factor (EGF) 5’UTR variant A61 G and melanoma/nevus susceptibility. J Invest Dermatol. 2004;123:755–759. doi:10.1111/j.0022-202X.2004.23304.x.

    Article  CAS  PubMed  Google Scholar 

  43. Kang HG, Choi JE, Lee WK, et al. +61A>G polymorphism in the EGF gene does not increase the risk of lung cancer. Respirology. 2007;12:902–905. doi:10.1111/j.1440-1843.2007.01152.x.

    Article  PubMed  Google Scholar 

  44. Goto Y, Ando T, Goto H, Hamajima N. No association between EGF gene polymorphism and gastric cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:2454–2456. doi:10.1158/1055-9965.EPI-05-0401.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Central Laboratory, The First Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, Peoples’ Republic of China

    Lin Cui & Hai-Bin Yu

  2. Department of Forensic Pathology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, Peoples’ Republic of China

    Xin-Min Pan

  3. Department of Gynecology, The Second Affiliated Hospital of Henan College of Traditional Chinese Medicine, Zhengzhou, 450003, Henan, Peoples’ Republic of China

    Chun-Fen Ma

  4. Institute for Immunization Programme, Jiangxi Province Center for Disease Control and Prevention, Nanchang, 330029, Jiangxi, Peoples’ Republic of China

    Jun Shang-Guan

  5. Department of Neurology, The People’s Hospital of Daye City, Daye, 435100, Hubei, Peoples’ Republic of China

    Guang-Xue Chen

  6. Department of Clinical Laboratory, Yan’an Hospital, Kunming, 650051, Yunnan, Peoples’ Republic of China

    Jia Wang

Authors
  1. Lin Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin-Min Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chun-Fen Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Shang-Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hai-Bin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guang-Xue Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xin-Min Pan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cui, L., Pan, XM., Ma, CF. et al. Association Between Epidermal Growth Factor Polymorphism and Esophageal Squamous Cell Carcinoma Susceptibility. Dig Dis Sci 55, 40–45 (2010). https://doi.org/10.1007/s10620-008-0700-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0700-5

Keywords

Search

Navigation