Skip to main content

Advertisement

SpringerLink
Log in

ERBB2 genetic polymorphism and breast cancer risk in Chinese women: a population-based case-control study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

A polymorphism at codon 655 (ATC/isoleucine to GTC/valine [Ile655Val], rs1801200) in the transmembrane domain-coding region of human ERBB2 gene has been previously evaluated for its association with breast cancer risk with mixed results. We evaluated this polymorphism in association with breast cancer in a group of women who participated in a large-scale, population-based, case-control study of breast cancer in Shanghai, China, followed by an in vitro analysis of the function of this polymorphism. Genomic DNA from 3,012 patients with breast cancer and 3,004 healthy controls was examined for the Ile655Val polymorphism using a TaqMan genotyping method. Adjusted odds ratios (OR) were derived from multiple logistic regression. In vitro analyses were carried out to examine whether the Ile655Val polymorphism affect ERBB2 expression and the activity of its downstream targets. Approximately 2% of study subjects carry the Val/Val genotype. Compared with women with the Ile/Ile (76%) genotype, women who had the Ile/Val (22%) or Val/Val genotype did not have an elevated risk of breast cancer. Stratified analyses by age and menopausal status revealed no apparent association with this polymorphism in any subgroups of women. In a serious of biochemical analyses, we found that the Ile655Val substitution did not alter ErbB2 and its downstream signaling molecule activity. These study results suggest that Ile655Val polymorphism of the ERBB2 gene do not alter its activity and may not be associated with increased breast cancer risk among Chinese women.

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

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CI:

Confidence interval

OR:

Odds ratios

BMI:

Body mass index

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptors

MAPK:

Mitogen-activated protein kinase

PI3K:

Phosphatidylinositol-3 kinase

PR:

Progesterone receptors

SBCS:

Shanghai Breast Cancer Study

TNM:

Tumor-node-metastasis

Reference

  1. Stern DF (2003) ErbBs in mammary development. Exp Cell Res 284:89–98

    Article  PubMed  CAS  Google Scholar 

  2. Holbro T et al (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284:99–110

    Article  PubMed  CAS  Google Scholar 

  3. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137

    Article  PubMed  CAS  Google Scholar 

  4. Pinkas-Kramarski R et al (1996) Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 15:2452–2467

    PubMed  CAS  Google Scholar 

  5. Slamon DJ et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712

    Article  PubMed  CAS  Google Scholar 

  6. Lemoine NR et al (1991) Amplification and overexpression of the EGF receptor and c-erbB-2 proto-oncogenes in human stomach cancer. Br J Cancer 64:79–83

    PubMed  CAS  Google Scholar 

  7. Revillion F et al (1998) ERBB2 oncogene in human breast cancer and its clinical significance. Eur J Cancer 34:791–808

    Article  PubMed  CAS  Google Scholar 

  8. Bargmann CI et al (1986) Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell 45:649–657

    Article  PubMed  CAS  Google Scholar 

  9. Muller WJ et al (1988) Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54:105–115

    Article  PubMed  CAS  Google Scholar 

  10. Guy CT et al (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 89:10578–10582

    Article  PubMed  CAS  Google Scholar 

  11. Saya H et al (1990) Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. Mol Carcinog 3:198–201

    Article  PubMed  CAS  Google Scholar 

  12. Lemoine NR et al (1990) Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. Oncogene 5:237–239

    PubMed  CAS  Google Scholar 

  13. Papewalis J et al (1991) G to A polymorphism at amino acid codon 655 of the human erbB-2/HER2 gene. Nucleic Acids Res 19:5452

    Article  PubMed  CAS  Google Scholar 

  14. Xie D et al (2000) Population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 92:412–417

    Article  PubMed  CAS  Google Scholar 

  15. Baxter SW Campbell IG (2001) Re: population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 93:557–559

    Article  Google Scholar 

  16. Hishida A et al (2002) Re: population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 94:1807–1808

    PubMed  CAS  Google Scholar 

  17. Keshava C et al (2001) Distribution of HER2(V655) genotypes in breast cancer cases and controls in the United States. Cancer Lett 173:37–41

    Article  PubMed  CAS  Google Scholar 

  18. Kean-Cowdin R et al (2001) Germ-line HER-2 variant and breast cancer risk by stage of disease. Cancer Res 61:8393–8394

    Google Scholar 

  19. Millikan R et al (2003) HER2 codon 655 polymorphism and risk of breast cancer in African Americans and whites. Breast Cancer Res Treat 79:355–364

    Article  PubMed  CAS  Google Scholar 

  20. Montgomery KG et al (2003) The HER2 I655V polymorphism and risk of breast cancer in women < age 40 years. Cancer Epidemiol Biomarkers Prev 12:1109–1111

    PubMed  CAS  Google Scholar 

  21. Wang-Gohrke S, Chang-Claude J (2001) Re: population-based, case-control study of HER2 genetic polymorphism and breast cancer risk. J Natl Cancer Inst 93:1657–1659

    Article  PubMed  CAS  Google Scholar 

  22. Nelson SE et al (2005) A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer. Breast Cancer Res 7:R357–R364

    Article  PubMed  CAS  Google Scholar 

  23. Zubor P et al (2006) HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia. Neoplasma 53:49–55

    PubMed  CAS  Google Scholar 

  24. Kamali-Sarvestani E et al (2004) Ile to Val polymorphism at codon 655 of HER-2 gene and breast cancer risk in Iranian women. Cancer Lett 215:83–87

    PubMed  CAS  Google Scholar 

  25. Gao YT et al (2000) Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study. Int J Cancer 87:295–300

    Article  PubMed  CAS  Google Scholar 

  26. Wang SE et al (2006) HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 10:25–38

    Article  PubMed  CAS  Google Scholar 

  27. Colditz GA, Baer H, Tamimi RM (2006) Breast cancer. In: Schottenfeld D, Fraumeni JF Jr (eds) Cancer epidemiology and prevention, 3rd edn. Oxford University Press, pp 995–1012

  28. Siegel PM et al (1994) Novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors. Mol Cell Biol 14:7068–7077

    PubMed  CAS  Google Scholar 

  29. Bargmann CI et al (1988) Oncogenic activation of the neuencoded receptor protein by point mutation and deletion. Embo J 7:2043–2052

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Jirong Long, Regina Courtney, Hongmei Wu, and Qing Wang for technical assistance in genotyping; Bethanie Hull and Brandy Venuti for assistance in the preparation of this article; as well as all study participants and research staff of the Shanghai Breast Cancer Study for their support. This research was supported by NIH grants RO1 CA64277 and RO1 CA90899 from the National Cancer Institute.

Author information

Authors and Affiliations

  1. Department of Medicine, Vanderbilt Epidemiology Center, Institute of Medicine and Public Health, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA

    Shimian Qu, Qiuyin Cai, Hui Cai, Yinghao Su, Xiao-Ou Shu & Wei Zheng

  2. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

    Yu-Tang Gao

  3. Shanghai Center for Disease Control and Prevention, Shanghai, China

    Wei Lu

  4. Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Shizhen Emily Wang

Authors
  1. Shimian Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiuyin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu-Tang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hui Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yinghao Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shizhen Emily Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiao-Ou Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Zheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qu, S., Cai, Q., Gao, YT. et al. ERBB2 genetic polymorphism and breast cancer risk in Chinese women: a population-based case-control study. Breast Cancer Res Treat 110, 169–176 (2008). https://doi.org/10.1007/s10549-007-9691-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-007-9691-8

Keywords

Search

Navigation