Skip to main content

Advertisement

SpringerLink
Log in

DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study

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

An Erratum to this article was published on 11 August 2013

Abstract

Aberrant DNA hypermethylation of gene promoter regions has been increasingly recognized as a common molecular alteration in carcinogenesis. We evaluated the association between major clinicopathological features and hypermethylation of genes in tumors among 803 incidence breast cancer cases from a large population-based case–control study conducted in Western New York State. DNA samples were isolated from archive paraffin embedded tumor tissue and were analyzed for hypermethylation status of the E-cadherin, p16, and RAR-β 2 genes using real time methylation-specific polymerase chain reaction. The frequencies of hypermethylation were 20.0% for E-cadherin, 25.9% for p16, and 27.5% for RAR-β 2 genes. For postmenopausal women, hypermethylation of E-cadherin tended to be more likely in progesterone receptor (PR) negative than in PR-positive tumors (odds ratio (OR), 1.41; 95% confidence interval (CI), 0.91–2.18). Hypermethylation of p16 tended to be more frequent among estrogen receptor (ER) negative cases than ER-positive cases (OR, 1.51; 95% CI, 1.01–2.32). Hypermethylation of RAR-β 2 gene was inversely associated with histological and nuclear grade of breast cancer.

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.

Similar content being viewed by others

References

  1. Wajed SA, Laird PW, DeMeester TR (2001) DNA methylation: an alternative pathway to cancer. Ann Surg 234:10–20

    Article  PubMed  CAS  Google Scholar 

  2. Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174

    Article  PubMed  CAS  Google Scholar 

  3. Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225–3229

    PubMed  CAS  Google Scholar 

  4. Esteller M, Silva JM, Dominguez G et al (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 92:564–569

    Article  PubMed  CAS  Google Scholar 

  5. Graff JR, Herman JG, Lapidus RG et al (1995) E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res 55:5195–5199

    PubMed  CAS  Google Scholar 

  6. Widschwendter M, Peter AJ (2002) DNA methylation and breast carcinogenesis. Oncogene 21:5462–5482

    Article  PubMed  CAS  Google Scholar 

  7. Raman V, Martensen SA, Reisman D et al (2000) Compromised HOXA5 function can limit p53 expression in human breast tumors. Nature 405:974–978

    Article  PubMed  CAS  Google Scholar 

  8. Wiley A, Katasaros D, Chen H et al (2006) Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential. Cancer 107:299–308

    Article  PubMed  CAS  Google Scholar 

  9. Toyota M, Ahuja N, Suzuki H et al (1999) Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Res 59:5438–5442

    PubMed  CAS  Google Scholar 

  10. Bannon K, Yanokura M, Susumu N et al (2006) Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer. Oncol Rep 16:1189–1196

    Google Scholar 

  11. Jeong DH, Youm MY, Kim YN et al (2006) Promoter methylation of p16, DAPK, CDH1, and TIMP-3 genes in cervical cancer: correlation with clinicopathologic characteristics. Int J Gynecol Cancer 16:1234–1240

    Article  PubMed  CAS  Google Scholar 

  12. Belinsky SA, Liechty KC, Gentry FD et al (2006) Promoter hypermthylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res 66:3338–3344

    Article  PubMed  CAS  Google Scholar 

  13. Bae YK, Brown A, Garrett E et al (2004) Hypermethylation in histologically distinct classes of breast cancer. Clin Cancer Res 10:5988–6005

    Article  Google Scholar 

  14. Li SY, Rong M, Iacopetta B (2006) DNA hypermethylation in breast cancer and its association with clinicopathological features. Cancer Lett 237:272–280

    Article  PubMed  CAS  Google Scholar 

  15. Shinozaki M, Hoon DSB, Giuliano AE et al (2005) Distinct hypermethylation profile of primary breast cancer is associated with sentinel lymph node metastasis. Clin Cancer Res 11:2156–2162

    Article  PubMed  CAS  Google Scholar 

  16. Parrella P, Poeta ML, Gallo AP et al (2004) Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors. Clin Cancer Res 10:5349–5354

    Article  PubMed  CAS  Google Scholar 

  17. Garcia JM, Silva J, Pena C et al (2004) Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosomes Cancer 41:117–124

    Article  PubMed  CAS  Google Scholar 

  18. Mehrotra J, Vali M, McVeigh M et al (2004) Very high frequency of hypermthylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res 10:3104–3109

    Article  PubMed  CAS  Google Scholar 

  19. Yan PS, Perry MR, Laux DE, Asare AL, Caldwell CW, Huang TH (2006) CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer. Clin Cancer Res 6:1432–1438

    Google Scholar 

  20. Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immumohistochemical analysis. Mod Pathol 11:155–168

    PubMed  CAS  Google Scholar 

  21. Tennis M, Krishnan S, Bonner M et al (2006) p53 Mutation analysis in breast tumors by a DNA microarray method. Cancer Epidemiol Biomarkers Prev 15:80–85

    Article  PubMed  CAS  Google Scholar 

  22. Jeronimo C, Usadel H, Henrique R et al (2001) Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma. J Natl Cancer Inst 93:1447–1452

    Article  Google Scholar 

  23. Harden SV, Tokumaru Y, Westra WH et al (2003) Gene promoter hypermethylation in tumors and lymph nodes of stage 1 lung cancer patients. Clin Cancer Res 9:1370–1375

    PubMed  CAS  Google Scholar 

  24. Usadel H, Brabender J, Danenberg KD et al (2002) Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer. Cancer Res 62:371–375

    PubMed  CAS  Google Scholar 

  25. Graff JR, Gabrelson E, Fujii H, Baylin SB, Herman JG (2000) Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem 275:2727–2732

    Article  PubMed  CAS  Google Scholar 

  26. Hazan NM, Qiao R, Keren R, Badano I, Suyama K (2004) Cadherin switch in tumor progression. Ann N Y Acad Sci 1014:155–163

    Article  PubMed  CAS  Google Scholar 

  27. Rieger-Christ KM, Pezza JA, Dugan JM et al (2001) Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas. Mol Pathol 54:91–97

    Article  PubMed  CAS  Google Scholar 

  28. More H, Humar B, Weber W et al (2007) Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene. Hum Mutat 28:203

    Article  PubMed  CAS  Google Scholar 

  29. Risinger JI, Berchuck A, Kohler MF, Boyd J (1994) Mutations of the E-cadherin gene in human gynecologic cancers. Nat Genet 7:98–102

    Article  PubMed  CAS  Google Scholar 

  30. Nass SJ, Herman JG, Gabrielson E et al (2000) Aberrant methylation of the estrogen receptor and E-cadherin 5′ CpG islands increases with malignant progression in human breast cancer. Cancer Res 60:4346–4348

    PubMed  CAS  Google Scholar 

  31. Droufakou S, Deshmane V, Roylance R, Hanby A, Tomlinson I, Hart IR (2001) Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast. Int J Cancer 92:404–408

    Article  PubMed  CAS  Google Scholar 

  32. Caldeira JR, Prando EC, Quevedo FC, Neto FA, Rainho CA, Rogatto SR (2006) CDH1 promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer. BMC Cancer 6:48

    Article  PubMed  Google Scholar 

  33. Lipponen P, Saarelainen E, Ji H, Aaltomaa S, Syrjanen K (1994) Expression of E-cadherin (E-CD) as related to other prognostic factors and survival in breast cancer. J Pathol 174:101–109

    Article  PubMed  CAS  Google Scholar 

  34. Charpin C, Garcia S, Bouvier C et al (1997) E-cadherin quantitative immunocytochemical assays in breast carcinomas. J Pathol 181:294–300

    Article  PubMed  CAS  Google Scholar 

  35. Sherr CJ (1996) Cancer cell cycles. Science 274:1672–1677

    Article  PubMed  CAS  Google Scholar 

  36. Tlsty TD, Crawford YG, Holst CR et al (2004) Genetic and epigenetic changes in mammary epithelial cells may mimic early events in carcinogenesis. J Mammary Gland Biol Neoplasia 9:263–274

    Article  PubMed  Google Scholar 

  37. Holst CR, Nuovo GJ, Esteller M et al (2003) Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epithelia. Cancer Res 63:1596–1601

    PubMed  CAS  Google Scholar 

  38. Lewis CM, Cler LR, Bu DW et al (2005) Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk. Clin Cancer Res 11:166–172

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study would not have been possible without the support of all of the study participants and research staff of the Western New York Exposures and Breast Cancer (WEB) Study. Funding This work was funded by United States Public Health Service (USPHS) Grant Number R01CA92585 from the National Cancer Institute, and #DAMD 17030446 and #DAMD 179616202 from the DOD.

Author information

Authors and Affiliations

  1. Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, 270 Farber Hall, Buffalo, NY, 14214, USA

    Meng Hua Tao, Jing Nie, Amy Millen, Dominica Vito, Maurizio Trevisan & Jo L. Freudenheim

  2. Lombardi Cancer Center, Georgetown University Medical Center, 3800 Reservoir RD. NW, LL (s) Level, Room 150, Box 571465, Washington, DC, 20057, USA

    Peter G. Shields, Shiva S. Krishnan, Catalin Marian & Bin Xie

  3. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA

    Christine B. Ambrosone & Stephen B. Edge

  4. Potomac Hospital, Woodbridge, VA, 22191, USA

    Janet Winston

Authors
  1. Meng Hua Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter G. Shields
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amy Millen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christine B. Ambrosone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stephen B. Edge
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shiva S. Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Catalin Marian
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bin Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Janet Winston
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dominica Vito
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maurizio Trevisan
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jo L. Freudenheim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Meng Hua Tao or Peter G. Shields.

Additional information

An erratum to this article can be found online at http://dx.doi.org/10.1007/s10549-013-2660-5.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tao, M.H., Shields, P.G., Nie, J. et al. DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat 114, 559–568 (2009). https://doi.org/10.1007/s10549-008-0028-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-008-0028-z

Keywords

Search

Navigation