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Polymorphism Arg290Arg in Esophageal-Cancer-Related Gene 1 (ECRG1) is a Prognostic Factor for Survival in Esophageal Cancer

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal-cancer-related gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma.

Methods

Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan–Meier method, multivariate Cox regression analysis, and odds ratio were determined. For all variables, cross tables were generated, followed by calculation of the p value by using the chi-square test/Fisher-exact test.

Results

Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a median follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%), and Gln290Gln in seven cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced overall survival (p = 0.01) and tumor-free survival (p = 0.01) by the log-rank test. Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant prognostic factor for survival (p = 0.012).

Conclusions

Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer.

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References

  1. Sugimachi K, Matsuoka H, Ohno S, Mori M, Kuwano H. Multivariate approach for assessing the prognosis of clinical oesophageal carcinoma. Br J Surg 1988;75:1115–1118. doi:10.1002/bjs.1800751122.

    Article  PubMed  CAS  Google Scholar 

  2. Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 1993;54:594–606. doi:10.1002/ijc.2910540413.

    Article  PubMed  CAS  Google Scholar 

  3. Wei JT, Shaheen N. The changing epidemiology of esophageal adenocarcinoma. Semin Gastrointest Dis 2003;14:112–127.

    PubMed  Google Scholar 

  4. Crew KD, Neugut AI. Epidemiology of upper gastrointestinal malignancies. Semin Oncol 2004;31:450–464. doi:10.1053/j.seminoncol.2004.04.021.

    Article  PubMed  Google Scholar 

  5. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005;97:142–146.

    Article  PubMed  Google Scholar 

  6. Lu SH, Chui SX, Yang WX, Hu XN, Guo LP, Li FM. Relevance of N-nitrosamines to oesophageal cancer in China. IARC Sci Publ 1991;105:11–17.

    PubMed  CAS  Google Scholar 

  7. Gao YT, McLaughlin JK, Blot WJ, Ji BT, Benichou J, Dai Q, et al. Risk factors for esophageal cancer in Shanghai, China. I. Role of cigarette smoking and alcohol drinking. Int J Cancer 1994;58:192–196. doi:10.1002/ijc.2910580208.

    Article  PubMed  CAS  Google Scholar 

  8. Franceschi S, Bidoli E, Negri E, Zambon P, Talamini R, Ruol A, et al. Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus. Int J Cancer 2000;86:626–631. doi:10.1002/(SICI)1097-0215(20000601)86:5<626::AID-IJC4>3.0.CO;2-Y.

    Article  PubMed  CAS  Google Scholar 

  9. Wong R, Malthaner R. Esophageal cancer: a systematic review. Curr Probl Cancer 2000;24:297–373. doi:10.1016/S0147-0272(00)80002-1.

    Article  PubMed  CAS  Google Scholar 

  10. Yang L, Parkin DM, Li L, Chen Y. Time trends in cancer mortality in China: 1987–1999. Int J Cancer 2003;106:771–83. doi:10.1002/ijc.11300.

    Article  PubMed  CAS  Google Scholar 

  11. Vallbohmer D, Lenz HJ. Predictive and prognostic molecular markers in outcome of esophageal cancer. Dis Esophagus 2006;19:425–432. doi:10.1111/j.1442-2050.2006.00622.x.

    Article  PubMed  CAS  Google Scholar 

  12. Zhao N, Wang J, Cui Y, Guo L, Lu SH. Induction of G1 cell cycle arrest and P15INK4b expression by ECRG1 through interaction with Miz-1. J Cell Biochem 2004;92:65–76. doi:10.1002/jcb.20025.

    Article  PubMed  CAS  Google Scholar 

  13. Su T, Liu H, Lu S. Cloning and identification of cDNA fragments related to human esophageal cancer. Zhonghua Zhong Liu Za Zhi 1998;20:254–257.

    PubMed  CAS  Google Scholar 

  14. Wang Y, Tang H, Lu S. Expression in E. coli of protein encoded by human esophageal cancer related gene-1. Zhonghua Zhong Liu Za Zhi 2000;22:198–200.

    PubMed  CAS  Google Scholar 

  15. Shiokawa M, Masutani M, Fujihara H, Ueki K, Nishikawa R, Sugimura T, et al. Genetic alteration of poly(ADP-ribose) polymerase-1 in human germ cell tumors. Jpn J Clin Oncol 2005;35:97–102. doi:10.1093/jjco/hyi028.

    Article  PubMed  Google Scholar 

  16. Li Y, Zhang X, Huang G, Miao X, Guo L, Lin D, et al. Identification of a novel polymorphism Arg290Gln of esophageal cancer related gene 1 (ECRG1) and its related risk to esophageal squamous cell carcinoma. Carcinogenesis 2006;27:798–802. doi:10.1093/carcin/bgi258.

    Article  PubMed  CAS  Google Scholar 

  17. Wittekind Ch MHJBFH. UICC (2002) TNM Klassifikation maligner Tumoren, 6.Aufl. Berlin: Springer, 2002.

    Google Scholar 

  18. Wittekind Ch KMSL. TNM Atlas. Illustrierter Leitfaden zur TNM/pTNM-Klassifikation maligner Tumoren. Berlin: Springer, 2005, pp 2511–2516.

    Google Scholar 

  19. Kuo KT, Chow KC, Wu YC, Lin CS, Wang HW, Li WY, et al. Clinicopathologic significance of cyclooxygenase-2 overexpression in esophageal squamous cell carcinoma. Ann Thorac Surg 2003;76:909–914. doi:10.1016/S0003-4975(03)00717-3.

    Article  PubMed  Google Scholar 

  20. Kulke MH, Odze RD, Mueller JD, Wang H, Redston M, Bertagnolli MM. Prognostic significance of vascular endothelial growth factor and cyclooxygenase 2 expression in patients receiving preoperative chemoradiation for esophageal cancer. J Thorac Cardiovasc Surg 2004;127:1579–1586. doi:10.1016/j.jtcvs.2003.12.034.

    Article  PubMed  CAS  Google Scholar 

  21. Xi H, Baldus SE, Warnecke-Eberz U, Brabender J, Neiss S, Metzger R, et al. High cyclooxygenase-2 expression following neoadjuvant radiochemotherapy is associated with minor histopathologic response and poor prognosis in esophageal cancer. Clin Cancer Res 2005;11:8341–8347. doi:10.1158/1078-0432.CCR-04-2373.

    Article  PubMed  CAS  Google Scholar 

  22. Fukai Y, Fukuchi M, Masuda N, Osawa H, Kato H, Nakajima T, et al. Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma. Int J Cancer 2003;104:161–166. doi:10.1002/ijc.10929.

    Article  PubMed  CAS  Google Scholar 

  23. Ikeda G, Isaji S, Chandra B, Watanabe M, Kawarada Y. Prognostic significance of biologic factors in squamous cell carcinoma of the esophagus. Cancer 1999;86:1396–1405. doi:10.1002/(SICI)1097-0142(19991015)86:8<1396::AID-CNCR3>3.0.CO;2-H.

    Article  PubMed  CAS  Google Scholar 

  24. Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, et al. p53 status and the efficacy of cancer therapy in vivo. Science 1994;266:807–810. doi:10.1126/science.7973635.

    Article  PubMed  CAS  Google Scholar 

  25. Kitamura K, Saeki H, Kawaguchi H, Araki K, Ohno S, Kuwano H, et al. Immunohistochemical status of the p53 protein and Ki-67 antigen using biopsied specimens can predict a sensitivity to neoadjuvant therapy in patients with esophageal cancer. Hepatogastroenterology 2000;47:419–423.

    PubMed  CAS  Google Scholar 

  26. Shimada Y, Watanabe G, Yamasaki S, Maeda M, Kawabe A, Kaganoi JI, et al. Histological response of cisplatin predicts patients' survival in oesophageal cancer and p53 protein accumulation in pretreatment biopsy is associated with cisplatin sensitivity. Eur J Cancer 2000;36:987–993. doi:10.1016/S0959-8049(00)00049-6.

    Article  PubMed  CAS  Google Scholar 

  27. Izzo JG, Wu TT, Wu X, Ensor J, Luthra R, Pan J, et al. Cyclin D1 guanine/adenine 870 polymorphism with altered protein expression is associated with genomic instability and aggressive clinical biology of esophageal adenocarcinoma. J Clin Oncol 2007;25:698–707. doi:10.1200/JCO.2006.08.0283.

    Article  PubMed  CAS  Google Scholar 

  28. Ikeguchi M, Maeta M, Kaibara N. Bax expression as a prognostic marker of postoperative chemoradiotherapy for patients with esophageal cancer. Int J Mol Med 2001;7:413–417.

    PubMed  CAS  Google Scholar 

  29. Sturm I, Petrowsky H, Volz R, Lorenz M, Radetzki S, Hillebrand T, et al. Analysis of p53/BAX/p16(ink4a/CDKN2) in esophageal squamous cell carcinoma: high BAX and p16(ink4a/CDKN2) identifies patients with good prognosis. J Clin Oncol 2001;19:2272–2281.

    PubMed  CAS  Google Scholar 

  30. Takayama T, Nagao M, Sawada H, Yamada Y, Emoto K, Fujimoto H, et al. Bcl-X expression in esophageal squamous cell carcinoma: association with tumor progression and prognosis. J Surg Oncol 2001;78:116–123. doi:10.1002/jso.1130.

    Article  PubMed  CAS  Google Scholar 

  31. Matsumoto M, Natsugoe S, Nakashima S, Okumura H, Sakita H, Baba M, et al. Clinical significance and prognostic value of apoptosis related proteins in superficial esophageal squamous cell carcinoma. Ann Surg Oncol 2001;8:598–604. doi:10.1007/s10434-001-0598-z.

    Article  PubMed  CAS  Google Scholar 

  32. Blessmann M, Kaifi JT, Schurr PG, Cihan A, Kalinin V, Trump F, et al. Short tandem repeat polymorphism in exon 4 of esophageal cancer related gene 2 predicts relapse of oral squamous cell carcinoma. Oral Oncol 2008;44:143–147.

    Article  PubMed  CAS  Google Scholar 

  33. Yue CM, Bi MX, Tan W, Deng DJ, Zhang XY, Guo LP, et al. Short tandem repeat polymorphism in a novel esophageal cancer-related gene (ECRG2) implicates susceptibility to esophageal cancer in Chinese population. Int J Cancer 2004;108:232–236. doi:10.1002/ijc.11560.

    Article  PubMed  CAS  Google Scholar 

  34. Kaifi JT, Rawnaq T, Schurr PG, Yekebas EF, Mann O, Merkert P, et al. Short tandem repeat polymorphism in exon 4 of esophageal cancer-related gene 2 detected in genomic DNA is a prognostic marker for esophageal cancer. Am J Surg 2007;194:380–384. doi:10.1016/j.amjsurg.2007.01.026.

    Article  PubMed  CAS  Google Scholar 

  35. Bernard-Gallon D, Bosviel R, Delort L, Fontana L, Chamoux A, Rabiau N, et al. DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk. Mol Cancer 2008;7:36. doi:10.1186/1476-4598-7-36.

    Article  PubMed  CAS  Google Scholar 

  36. Sharifi R, Allameh A, Biramijamal F, Mohammadzadeh SH, Rasmi Y, Tavangar SM, et al. Relationship between genetic polymorphism of glutathione S-transferase-p1 and p53 protein accumulation in Iranian esophageal squamous cell carcinoma patients. Indian J Cancer 2008;45:8–12.

    Article  PubMed  CAS  Google Scholar 

  37. Han SG, Park KH, Sung JS, Whang YM, Kim YJ, Shin ES, et al. Single nucleotide polymorphisms of IGFBP-3 gene and lung cancer risk in a Korean population. Lung Cancer 2008;62:152–161.

    Article  PubMed  Google Scholar 

  38. Wang V, Chuang TC, Soong BW, Shan DE, Kao MC. Octarepeat changes of prion protein in Parkinson's disease. Parkinsonism Relat Disord 2008; in press, May 1.

  39. Netzel-Arnett S, Hooper JD, Szabo R, Madison EL, Quigley JP, Bugge TH, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev 2003;22:237–258. doi:10.1023/A:1023003616848.

    Article  PubMed  CAS  Google Scholar 

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Bachmann, K., Shahmiri, S., Kaifi, J. et al. Polymorphism Arg290Arg in Esophageal-Cancer-Related Gene 1 (ECRG1) is a Prognostic Factor for Survival in Esophageal Cancer. J Gastrointest Surg 13, 181–187 (2009). https://doi.org/10.1007/s11605-008-0766-6

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  • DOI: https://doi.org/10.1007/s11605-008-0766-6

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