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Tumor Biology

, Volume 37, Issue 6, pp 7239–7244 | Cite as

Association of HER2 codon 655 polymorphism with ovarian cancer

  • Rafał Watrowski
  • Dan Cacsire Castillo-Tong
  • Eva Schuster
  • Michael B. Fischer
  • Paul Speiser
  • Robert Zeillinger
Original Article

Abstract

The role of the human epidermal growth factor receptor 2 (HER2) codon 655 (Ile655Val) polymorphism in ovarian cancer is not fully understood. Two studies indicated a possible association between the Val allele and elevated risk or reduced prognosis of ovarian cancer. We investigated the HER2 codon 655 (rs1136201) polymorphism in 242 Austrian women—142 ovarian cancer patients and 100 healthy controls—by polymerase chain reaction and pyrosequencing. Associations between Ile655Val polymorphism and clinicopathological variables (e.g., age, FIGO stage, grading, serous vs. non-serous histology) were evaluated. The genotype distributions in ovarian cancer patients and controls were: AA; 66.2 %, AG; 25.35 %, GG; 8.45 %, and AA; 63 %, AG; 34 %, GG; 3.7 %, respectively (OR 1.15, CI 95 % 0.67–1.96). We observed a non-significant trend toward elevated cancer risk in Val/Val genotype (OR 2.98, CI 95 % 0.82–10.87, p = 0.10). Of note, 11 out of 12 Val/Val homozygotes were postmenopausal. The link between the Val/Val homozygosity and age over 50 years at diagnosis (OR 0.15, CI 95 % 0.02–1.2) was barely significant (p = 0.056). Summarizing, our data indicated a non-significant trend toward increased ovarian cancer risk in the Val/Val homozygosity, especially in women aged above 50 years. Further large-cohort studies focusing on the role of the HER2 codon 655 Val allele are needed.

Keywords

HER2 Codon 655 HER2 Ile655Val Ovarian cancer Polymorphism 

Notes

Acknowledgments

RW was supported by the Ernst Mach Grant of the Austrian Exchange Service (ÖAD) financed by the Austrian Ministry of Education, Science and Culture (BMBWK).

Compliance with ethical standards

Conflicts of interest

None.

References

  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Lowe KA, Chia VM, Taylor A, O’Malley C, Kelsh M, Mohamed M, et al. An international assessment of ovarian cancer incidence and mortality. Gynecol Oncol. 2013;130:107–14.CrossRefPubMedGoogle Scholar
  3. 3.
    American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol. 2007;110:201–14.CrossRefGoogle Scholar
  4. 4.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Reese DM, Slamon DJ. HER-2/neu signal transduction in human breast and ovarian cancer. Stem Cells. 1997;15:1–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Ferretti G, Felici A, Papaldo P, Fabi A, Cognetti F. HER2/neu role in breast cancer: from a prognostic foe to a predictive friend. Curr Opin Obstet Gynecol. 2007;19:56–62.CrossRefPubMedGoogle Scholar
  7. 7.
    Liang JW, Zhang JJ, Zhang T, Zheng ZC. Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature. Tumour Biol. 2014;35:4849–58.CrossRefPubMedGoogle Scholar
  8. 8.
    Gu J, Zheng L, Wang Y, Zhu M, Wang Q, Li X. Prognostic significance of HER2 expression based on trastuzumab for gastric cancer (ToGA) criteria in gastric cancer: an updated meta-analysis. Tumour Biol. 2014;35:5315–21.CrossRefPubMedGoogle Scholar
  9. 9.
    Gu J, Zheng L, Zhang L, Chen S, Zhu M, Li X, et al. TFF3 and HER2 expression and their correlation with survival in gastric cancer. Tumour Biol. 2015;36:3001–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Otsu H, Oki E, Ikawa-Yoshida A, Kawano H, Ando K, Ida S, et al. Correlation of HER2 expression with clinicopathological characteristics and prognosis in resectable gastric cancer. Anticancer Res. 2015;35:2441–6.PubMedGoogle Scholar
  11. 11.
    Wu SW, Ma CC, Yang Y. The prognostic value of HER-2/neu overexpression in colorectal cancer: evidence from 16 studies. Tumour Biol. 2014;35:10799–804.CrossRefPubMedGoogle Scholar
  12. 12.
    Ingold Heppner B, Behrens HM, Balschun K, Haag J, Krüger S, Becker T, et al. HER2/neu testing in primary colorectal carcinoma. Br J Cancer. 2014;111:1977–84.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Han J, Meng QY, Liu X, Xi QL, Zhuang QL, Wu GH. Lack of effects of HER-2/neu on prognosis in colorectal cancer: a meta-analysis. Asian Pac J Cancer Prev. 2014;15:5551–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMedGoogle Scholar
  15. 15.
    Wei Q, Xu J, Shen L, Fu X, Zhang B, Zhou X, et al. HER2 expression in primary gastric cancers and paired synchronous lymph node and liver metastases. A possible road to target HER2 with radionuclides. Tumour Biol. 2014;35:6319–26.CrossRefPubMedGoogle Scholar
  16. 16.
    Camilleri-Broët S, Hardy-Bessard AC, Le Tourneau A, Paraiso D, Levrel O, Leduc B, et al. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann Oncol. 2004;15:104–12.CrossRefPubMedGoogle Scholar
  17. 17.
    Pils D, Pinter A, Reibenwein J, Alfanz A, Horak P, Schmid BC, et al. In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway. Br J Cancer. 2007;96:485–91.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tuefferd M, Couturier J, Penault-Llorca F, Vincent-Salomon A, Broët P, Guastalla JP, et al. HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients. PLoS One. 2007;2:e1138.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Demir L, Yigit S, Sadullahoglu C, Akyol M, Cokmert S, Kucukzeybek Y, et al. Hormone receptor, HER2/NEU and EGFR expression in ovarian carcinoma—is here a prognostic phenotype? Asian Pac J Cancer Prev. 2014;15:9739–45.CrossRefPubMedGoogle Scholar
  20. 20.
    Wang Y, Wang D, Ren M. Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a meta-analysis. Tumour Biol. 2014;35:33–8. doi: 10.1007/s13277-013-1003-9.CrossRefPubMedGoogle Scholar
  21. 21.
    Teplinsky E, Muggia F. Targeting HER2 in ovarian and uterine cancers: challenges and future directions. Gynecol Oncol. 2014;135:364–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Papewalis J, Nikitin AY, Rajewsky MF. G to A polymorphism at amino acid codon 655 of the human erbB-2/HER2 gene. Nucleic Acids Res. 1991;19:5452.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    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;99:15937–40.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Pinto D, Pereira D, Portela C, da Silva JL, Lopes C, Medeiros R. The influence of HER2 genotypes as molecular markers in ovarian cancer outcome. Biochem Biophys Res Commun. 2005;335:1173–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Puputti M, Sihto H, Isola J, Butzow R, Joensuu H, Nupponen NN. Allelic imbalance of HER2 variant in sporadic breast and ovarian cancer. Cancer Genet Cytogenet. 2006;167:32–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Mojtahedi Z, Erfani N, Malekzadeh M, Haghshenas MR, Ghaderi A, Samsami DA. HER2 Ile655Val single nucleotide polymorphism in patients with ovarian cancer. Iran Red Crescent Med J. 2013;15:1–3.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Shanmughapriya S, Senthilkumar G, Arun S, Vinodhini K, Sudhakar S, Natarajaseenivasan K. Polymorphism and overexpression of HER2/neu among ovarian carcinoma women from Tiruchirapalli, Tamil Nadu. India Arch Gynecol Obstet. 2013;288:1385–90.CrossRefPubMedGoogle Scholar
  28. 28.
    Tavassoli FA, Devilee P, editors. World health organization classification of tumours: pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press; 2003.Google Scholar
  29. 29.
    Pecorelli S, Benedet JL, Creasman WT, Shepherd JH. FIGO staging of gynecologic cancer. Int J Gynaecol Obstet. 1999;65:243–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Hardy-Weinberg Equilibrium Calculator for 2 Alleles. http://www.had2know.com/academics/hardy-weinberg-equilibrium-calculator-2-alleles.html Accessed 24 Aug 2015
  31. 31.
    Lowry R. Vassar Stats: Website for Statistical Computation. http://vassarstats.net . Accessed 24 Aug 2015
  32. 32.
    Lu S, Wang Z, Liu H, Hao X. HER2 Ile655Val polymorphism contributes to breast cancer risk: evidence from 27 case-control studies. Breast Cancer Res Treat. 2010;124:771–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Dahabreh IJ, Murray S. Lack of replication for the association between HER2 I655V polymorphism and breast cancer risk: a systematic review and meta-analysis. Cancer Epidemiol. 2011;35:503–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Ma Y, Yang J, Zhang P, Liu Z, Yang Z, Qin H. Lack of association between HER2 codon 655 polymorphism and breast cancer susceptibility: meta-analysis of 22 studies involving 19,341 subjects. Breast Cancer Res Treat. 2011;125:237–41.CrossRefPubMedGoogle Scholar
  35. 35.
    Wang H, Liu L, Lang Z, Guo S, Gong H, Guan H, et al. Polymorphisms of ERBB2 and breast cancer risk: a meta-analysis of 26 studies involving 35,088 subjects. J Surg Oncol. 2013;108:337–41.CrossRefPubMedGoogle Scholar
  36. 36.
    Zúbor P, Vojvodová A, Danko J, Kajo K, Szunyogh N, Lasabová Z, et al. HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case–control study in Slovakia. Neoplasma. 2006;53:49–55.PubMedGoogle Scholar
  37. 37.
    Zubor P, Kajo K, Stanclova A, Szunyogh N, Galo S, Dussan CA, et al. Human epithelial growth factor receptor 2 [Ile655Val] polymorphism and risk of breast fibroadenoma. Eur J Cancer Prev. 2008;17:33–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Watrowski R, Castillo-Tong DC, Wolf A, Schuster E, Fischer MB, Speiser P, et al. HER2 Codon 655 (Ile/Val) polymorphism and breast cancer in Austrian women. Anticancer Res. 2015;35:5901–4.PubMedGoogle Scholar
  39. 39.
    Kruszyna Ł, Lianeri M, Roszak A, Jagodziński PP. HER2 codon 655 polymorphism is associated with advanced uterine cervical carcinoma. Clin Biochem. 2010;43:545–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Mishra K, Behari A, Kapoor VK, Khan MS, Prakash S, Agrawal S. Platelet derived growth factor-B and human epidermal growth factor receptor-2 polymorphisms in gall bladder cancer. Asian Pac J Cancer Prev. 2015;16:5647–54.CrossRefPubMedGoogle Scholar
  41. 41.
    Mutluhan H, Akbas E, Erdogan NE, Soylemez F, Senli MS, Polat A, et al. The influence of HER2 genotypes as molecular markers on breast cancer outcome. DNA Cell Biol. 2008;27:575–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Millikan R, Eaton A, Worley K, Biscocho L, Hodgson E, Huang WY, et al. HER2 codon 655 polymorphism and risk of breast cancer in African Americans and whites. Breast Cancer Res Treat. 2003;79:355–64.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Rafał Watrowski
    • 1
    • 2
  • Dan Cacsire Castillo-Tong
    • 2
  • Eva Schuster
    • 2
  • Michael B. Fischer
    • 3
  • Paul Speiser
    • 2
  • Robert Zeillinger
    • 2
  1. 1.Department of Gynecology and Obstetrics, St. JosefskrankenhausTeaching Hospital of the University of FreiburgFreiburgGermany
  2. 2.Department of Obstetrics and Gynecology, Molecular Oncology GroupMedical University of ViennaViennaAustria
  3. 3.Department of Blood Group Serology and Transfusion MedicineMedical University of ViennaViennaAustria

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