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Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2 Gene Polymorphisms in Endometrial Cancer in a Japanese Population

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Abstract

Endometrial cancer is associated with both EGFR and HER2 receptor activation. The EGFR and HER2 genes could be disease susceptibility candidate genes for this cancer. This study was conducted to investigate a possible association between EGFR and HER2 gene polymorphisms and endometrial cancer and the influence of these polymorphisms on the clinical outcome of endometrial cancer patients in a Japanese population. The authors compare the genotype distributions and allele frequencies of the EGFR +2073 A/T and HER2 +655 A/G polymorphisms in 116 endometrial cancer patients and 213 controls using polymerase chain reaction—restriction fragment length polymorphism (RFLP) analysis. RFLP results were confirmed by direct DNA sequencing. Of the 116 patients, 76 (65.5%) could be followed up. Disease-free survival estimates were computed using the Kaplan-Meier method, and differences between survival periods were assessed using the log-rank test. No significant differences were observed in either genotype distributions or allele frequencies in the EGFR +2073 A/T and HER2 +655 A/G polymorphisms between endometrial cancer patients and controls. The stratification by histological types and staging failed to identify significant differences between endometrial cancer patients and controls. No statistical differences were noted between these polymorphisms and disease-free survival (Kaplan-Meier log-rank test P = .55 and .66, for the EGFR +2073 A/T and HER2 +655 A/G, respectively). These results suggest that the EGFR +2073 A/T and HER2 +655 A/G polymorphisms are not associated with endometrial cancer in a Japanese population. These conclusions are based on relatively small numbers and will require verification from additional independent studies.

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References

  1. Persson I, Adami HO, Bergkvist L, et al. Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study. BMJ. 1989;298:147–151.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sherman MET. heories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol. 2000;13:295–308.

    Article  CAS  PubMed  Google Scholar 

  3. Emons G, Fleckenstein G, Hinney B, Huschmand A, Heyl W. Hormonal interactions in endometrial cancer. Endocr Relat Cancer. 2000;7:227–242.

    CAS  Google Scholar 

  4. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000;19:3159–3167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Laskin JJ, Sandler AB. Epidermal growth factor receptor: a promising target in solid tumours. Cancer Treat Rev. 2004;30:1–17.

    Article  CAS  PubMed  Google Scholar 

  6. Goldstein NS, Armin M. Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer. 2001;92:1331–1346.

    Article  CAS  PubMed  Google Scholar 

  7. Uegaki K, Nio Y, Inoue Y, et al. Clinicopathological significance of epidermal growth factor and its receptor in human pancreatic cancer. Anticancer Res. 1997;17:3841–3847.

    CAS  PubMed  Google Scholar 

  8. Rusch V, Klimstra D, Venkatraman E, Pisters PW, Langenfeld J, Dmitrovsky E. Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor α is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res. 1997;3:515–522.

    CAS  PubMed  Google Scholar 

  9. Bartlett JM, Langdon SP, Simpson BJ, et al. The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer. Br J Cancer. 1996;73:301–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Walker RA, Dearing SJ. Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas. Breast Cancer Res Treat. 1999;53:167–176.

    Article  CAS  PubMed  Google Scholar 

  11. Rubin Grandis J, Melhem MF, Gooding WE, et al. Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst. 1998;90:824–832.

    Article  CAS  PubMed  Google Scholar 

  12. Volm M, Rittgen W, Drings P. Prognostic value of ERBB-1, VEGF, cyclin A, FOS, JUN and MYC in patients with squamous cell lung carcinomas. Br J Cancer. 1998;77:663–669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Plowman GD, Whitney GS, Neubauer MG, et al. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci U S A. 1990; 87:4905–4909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Plowman GD, Culouscou JM, Whitney GS, et al. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993;90:1746–1750.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kuan CT, Wikstrand CJ, Bigner DD. EGF mutant receptor vIII as a molecular target in cancer therapy. Endocr Relat Cancer. 2001;8:83–96.

    Article  CAS  PubMed  Google Scholar 

  16. Khalifa MA, Abdoh AA, Mannel RS, Haraway SD, Walker JL, Min KW. Prognostic utility of epidermal growth factor receptor overexpression in endometrial adenocarcinoma. Cancer. 1994;73:370–376.

    Article  CAS  PubMed  Google Scholar 

  17. Wang D, Konishi I, Koshiyama M, et al. Expression of c-erbB-2 protein and epidermal growth receptor in endometrial carcinomas: correlation with clinicopathologic and sex steroid receptor status. Cancer. 1993;72:2628–2637.

    Article  CAS  PubMed  Google Scholar 

  18. Brandt B, Hermann S, Straif K, Tidow N, Buerger H, Chang-Claude J. Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene. Cancer Res. 2004;64:7–12.

    Article  CAS  PubMed  Google Scholar 

  19. Bast RC Jr, Pusztai L, Kerns BJ, et al. Coexpression of the HER-2 gene product, p185HER-2, and epidermal growth factor receptor, p170EGF-R, on epithelial ovarian cancers and normal tissues. Hybridoma. 1998;17:313–321.

    Article  CAS  PubMed  Google Scholar 

  20. Goel S, Mani S, Perez-Soler R. Tyrosine kinase inhibitors: a clinical perspective. Curr Oncol Rep. 2002;4:9–19.

    Article  PubMed  Google Scholar 

  21. Hynes NE, Stern DF. The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta. 1994;1198:165–184.

    PubMed  Google Scholar 

  22. Riben MW, Malfetano JH, Nazeer T, Muraca PJ, Ambros RA, Ross JS. Identification of HER-2/neu oncogene amplification by fluorescence in situ hybridization in stage I endometrial carcinoma. Mod Pathol 1997; 10: 823–31.

    CAS  PubMed  Google Scholar 

  23. Rolitsky CD, Theil KS, McGaughy VR, Copeland LJ, Niemann TH. HER-2/neu amplification and overexpression in endometrial carcinoma. Int J Gynecol Pathol. 1999;18:138–143.

    Article  CAS  PubMed  Google Scholar 

  24. Eccles SA, Modjtahedi H, Box G, Court W, Sandle J, Dean CJ. Significance of the c-erbB family of receptor tyrosine kinases in metastatic cancer and their potential as targets for immunotherapy. Invasion Metastasis. 1994–1995;14:337–348.

    CAS  PubMed  Google Scholar 

  25. Berchuck A, Rodriguez G, Kinney RB, et al. Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. Am J Obstet Gynecol. 1991;164:15–21.

    Article  CAS  PubMed  Google Scholar 

  26. Hetzel DJ, Wilson TO, Keeney GL, Roche PC, Cha SS, Podratz KC. HER-2/neu expression: a major prognostic factor in endometrial cancer. Gynecol Oncol. 1992;47:179–185.

    Article  CAS  PubMed  Google Scholar 

  27. De Bortoli M, Maggiora P, Capello D, et al. Hormonal control of growth factor receptor expression. Ann N Y Acad Sci. 1996;784:336–348.

    Article  PubMed  Google Scholar 

  28. Kuraoka K, Matsumura S, Hamai Y, et al. A single nucleotide polymorphism in the transmembrane domain coding region of HER-2 is associated with development and malignant phenotype of gastric cancer. Int J Cancer. 2003;107:593–596.

    Article  CAS  PubMed  Google Scholar 

  29. Ameyaw MM, Tayeb M, Thornton N, et al. Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer. J Hum Genet. 2002;47:172–175.

    Article  CAS  PubMed  Google Scholar 

  30. Shintani S, Matsuo K, Crohin CC, et al. Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes. Cancer Res. 1999;59:4142–4147.

    CAS  PubMed  Google Scholar 

  31. Hsieh YY, Chang CC, Tsai FJ, Lin CC, Tsai CH. T homozygote and allele of epidermal growth factor receptor 2073 gene polymorphism are associated with higher susceptibility to endometriosis and leiomyomas. Fertil Steril. 2005;83:796–799.

    Article  CAS  PubMed  Google Scholar 

  32. Huang CM, Tsai CH, Chen CL, Chang CP, Lai CC, Tsai FJ. Epidermal growth factor receptor (EGFR) gene Bsr I polymorphism is associated with systemic lupus erythematosus. Lupus. 2004;13:773–776.

    Article  CAS  PubMed  Google Scholar 

  33. Xie D, Shu XO, Deng Z, et al. Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst. 2000;92:412–417.

    Article  CAS  PubMed  Google Scholar 

  34. Yokomizo A, Koga H, Kinukawa N, et al. Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility. Prostate. 2005;62:49–53.

    Article  CAS  PubMed  Google Scholar 

  35. Wang L, Habuchi T, Takahashi T, et al. No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer. Int J Cancer. 2002;97:787–790.

    Article  CAS  PubMed  Google Scholar 

  36. Ueda M, Hung YC, Terai Y, et al. HER-2 codon 655 polymorphism in cervical carcinogenesis. Int J Gynecol Cancer. 2006;16:325–328.

    Article  CAS  PubMed  Google Scholar 

  37. An HJ, Kim NK, Oh D, et al. Her2V655 genotype and breast cancer progression in Korean women. Pathol Int. 2005;55:48–52.

    Article  CAS  PubMed  Google Scholar 

  38. McKay JA, Loane JF, Ross VG, et al. c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002;86:568–573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Millikan R, Eaton A, Worley K, et al. HER2 codon 655 polymorphism and risk of breast cancer in African Americans and whites. Breast Cancer Res Treat. 2003;79:355–364.

    Article  CAS  PubMed  Google Scholar 

  40. Cox DG, Hankinson SE, Hunter DJ. The erbB2/HER2/neu receptor polymorphism Ile655Val and breast cancer risk. Pharmacogenet Genomics. 2005;15:447–450.

    CAS  Google Scholar 

  41. Fleishman SJ, Schlessinger J, Ben-Tal N. A putative molecular-activation switch in the transmembrane domain of erbB2. Proc Natl Acad Sci U S A. 2002;99:15937–15940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Papewalis J, Nikitin AYu, Rajewsky MF. G to A polymorphism at amino acid codon 655 of the human erbB-2/HER2 gene. Nucleic Acids Res. 1991;19:5452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Prat J, Oliva E, Lerma E, Vaquero M, Matias-Guiu X. Uterine papillary serous adenocarcinoma: a 10-case study of p53 and c-erbB-2 expression and DNA content. Cancer. 1994;74:1778–1783.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Shigeki Yoshida MD, PhD.

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This work was supported by a Grant-in-Aid for Scientific Research (16024212) from the Japanese Ministry of Education, Science and Culture.

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Kitao, K., Yoshida, S., Kennedy, S. et al. Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor 2 Gene Polymorphisms in Endometrial Cancer in a Japanese Population. Reprod. Sci. 14, 349–357 (2007). https://doi.org/10.1177/1933719107303383

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