Home LiteratureArticle Details
PMID: 18463976 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

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

Breast cancer research and treatment ·Vol. 114 ·No. 3 ·2009-04-00 ·Pages 559-68

Tao MH, Shields PG, Nie J, Millen A, Ambrosone CB, Edge SB, Krishnan SS, Marian C, Xie B, Winston J, Vito D, Trevisan M, Freudenheim JL

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-beta(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-beta(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-beta(2) gene was inversely associated with histological and nuclear grade of breast cancer.

MeSH Terms
Adult Aged Breast Neoplasms/epidemiology,etiology,genetics Cadherins/biosynthesis,genetics Case-Control Studies Cyclin-Dependent Kinase Inhibitor p16 DNA Methylation Gene Expression Regulation, Neoplastic Humans Middle Aged Neoplasm Metastasis Neoplasm Proteins/biosynthesis,genetics New York Postmenopause Receptors, Progesterone/biosynthesis,genetics Receptors, Retinoic Acid/biosynthesis,genetics Reverse Transcriptase Polymerase Chain Reaction
Chemicals
CDKN2A protein, human Cadherins Cyclin-Dependent Kinase Inhibitor p16 Neoplasm Proteins RARB2 protein, human Receptors, Progesterone Receptors, Retinoic Acid
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Tao Meng Hua
Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, USA. [email protected]
Shields Peter G
Nie Jing
Millen Amy
Ambrosone Christine B
Edge Stephen B
Krishnan Shiva S
Marian Catalin
Xie Bin
Winston Janet
Vito Dominica
Trevisan Maurizio
Freudenheim Jo L
References (38)
38 references, click to expand
  1. Hypermethylation in histologically distinct classes of breast cancer.
    Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):5998-6005 PMID: 15447983
  2. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype.
    Cancer Res. 1999 Nov 1;59(21):5438-42 PMID: 10554013
  3. 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. 2000 Jan 28;275(4):2727-32 PMID: 10644736
  4. CDH1 promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer.
    BMC Cancer. 2006 Mar 02;6:48 PMID: 16512896
  5. Gene promoter hypermethylation in tumors and lymph nodes of stage I lung cancer patients.
    Clin Cancer Res. 2003 Apr;9(4):1370-5 PMID: 12684406
  6. Genetic and epigenetic changes in mammary epithelial cells may mimic early events in carcinogenesis.
    J Mammary Gland Biol Neoplasia. 2004 Jul;9(3):263-74 PMID: 15557799
  7. DNA hypermethylation in tumorigenesis: epigenetics joins genetics.
    Trends Genet. 2000 Apr;16(4):168-74 PMID: 10729832
  8. Compromised HOXA5 function can limit p53 expression in human breast tumours.
    Nature. 2000 Jun 22;405(6789):974-8 PMID: 10879542
  9. E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas.
    Cancer Res. 1995 Nov 15;55(22):5195-9 PMID: 7585573
  10. Disparate E-cadherin mutations in LCIS and associated invasive breast carcinomas.
    Mol Pathol. 2001 Apr;54(2):91-7 PMID: 11322170
  11. Expression of E-cadherin (E-CD) as related to other prognostic factors and survival in breast cancer.
    J Pathol. 1994 Oct;174(2):101-9 PMID: 7965405
  12. p53 Mutation analysis in breast tumors by a DNA microarray method.
    Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):80-5 PMID: 16434591
  13. Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung.
    Clin Cancer Res. 2004 May 1;10(9):3104-9 PMID: 15131050
  14. DNA hypermethylation in breast cancer and its association with clinicopathological features.
    Cancer Lett. 2006 Jun 18;237(2):272-80 PMID: 16029926
  15. Mutations of the E-cadherin gene in human gynecologic cancers.
    Nat Genet. 1994 May;7(1):98-102 PMID: 8075649
  16. A gene hypermethylation profile of human cancer.
    Cancer Res. 2001 Apr 15;61(8):3225-9 PMID: 11309270
  17. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors.
    J Natl Cancer Inst. 2000 Apr 5;92(7):564-9 PMID: 10749912
  18. Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort.
    Cancer Res. 2006 Mar 15;66(6):3338-44 PMID: 16540689
  19. Cadherin switch in tumor progression.
    Ann N Y Acad Sci. 2004 Apr;1014:155-63 PMID: 15153430
  20. DNA methylation: an alternative pathway to cancer.
    Ann Surg. 2001 Jul;234(1):10-20 PMID: 11420478
  21. Promoter methylation of p16, DAPK, CDH1, and TIMP-3 genes in cervical cancer: correlation with clinicopathologic characteristics.
    Int J Gynecol Cancer. 2006 May-Jun;16(3):1234-40 PMID: 16803511
  22. Promoter methylation of the PTEN gene is a common molecular change in breast cancer.
    Genes Chromosomes Cancer. 2004 Oct;41(2):117-24 PMID: 15287024
  23. E-cadherin quantitative immunocytochemical assays in breast carcinomas.
    J Pathol. 1997 Mar;181(3):294-300 PMID: 9155715
  24. Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors.
    Clin Cancer Res. 2004 Aug 15;10(16):5349-54 PMID: 15328171
  25. Promoter hypermethylation in benign breast epithelium in relation to predicted breast cancer risk.
    Clin Cancer Res. 2005 Jan 1;11(1):166-72 PMID: 15671542
  26. DNA methylation and breast carcinogenesis.
    Oncogene. 2002 Aug 12;21(35):5462-82 PMID: 12154408
  27. Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer.
    Cancer Res. 2002 Jan 15;62(2):371-5 PMID: 11809682
  28. Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma.
    J Natl Cancer Inst. 2001 Nov 21;93(22):1747-52 PMID: 11717336
  29. Distinct hypermethylation profile of primary breast cancer is associated with sentinel lymph node metastasis.
    Clin Cancer Res. 2005 Mar 15;11(6):2156-62 PMID: 15788661
  30. Aberrant promoter methylation of multiple genes in malignant ovarian tumors and in ovarian tumors with low malignant potential.
    Cancer. 2006 Jul 15;107(2):299-308 PMID: 16773633
  31. Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epithelia.
    Cancer Res. 2003 Apr 1;63(7):1596-601 PMID: 12670910
  32. Multiple ways of silencing E-cadherin gene expression in lobular carcinoma of the breast.
    Int J Cancer. 2001 May 1;92(3):404-8 PMID: 11291078
  33. CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer.
    Clin Cancer Res. 2000 Apr;6(4):1432-8 PMID: 10778974
  34. Aberrant methylation of the estrogen receptor and E-cadherin 5' CpG islands increases with malignant progression in human breast cancer.
    Cancer Res. 2000 Aug 15;60(16):4346-8 PMID: 10969774
  35. Cancer cell cycles.
    Science. 1996 Dec 6;274(5293):1672-7 PMID: 8939849
  36. Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer.
    Oncol Rep. 2006 Dec;16(6):1189-96 PMID: 17089036
  37. Prognostic and predictive factors in breast cancer by immunohistochemical analysis.
    Mod Pathol. 1998 Feb;11(2):155-68 PMID: 9504686
  38. Identification of seven novel germline mutations in the human E-cadherin (CDH1) gene.
    Hum Mutat. 2007 Feb;28(2):203 PMID: 17221870
Article Info
Journal
Breast cancer research and treatment
Abbr.
Breast Cancer Res Treat
ISSN
1573-7217
DOI
10.1007/s10549-008-0028-z
Email
[email protected]
Published
2009-04-00
Epub
2008-00-08
Pages
559-68
Language
English
Region
Netherlands
NLM ID
8111104
PMCID
PMC4408917
Subset
IM
Grants
NCI NIH HHS · R01 CA092585 · United States
NCI NIH HHS · R01CA092040 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1007/s10549-008-0028-z PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2