DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study.
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.
Tao
Meng Hua
MH
Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, 270 Farber Hall, Buffalo, NY 14214, USA. mtao@buffalo.edu
Shields
Peter G
PG
Nie
Jing
J
Millen
Amy
A
Ambrosone
Christine B
CB
Edge
Stephen B
SB
Krishnan
Shiva S
SS
Marian
Catalin
C
Xie
Bin
B
Winston
Janet
J
Vito
Dominica
D
Trevisan
Maurizio
M
Freudenheim
Jo L
JL
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009518:New York; D017698:Postmenopause; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000614131:CDKN2A protein, human; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; C533416:RARB2 protein, human; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid