title: DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study.
abstract: We evaluated the association between methylation of 9 genes, SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1, and SFN in tumor samples from 720 breast cancer cases with clinicopathological features of the tumors and survival. Logistic regression was used to estimate odds ratios (OR) of methylation and Cox proportional hazards models to estimate hazard ratios (HR) between methylation and breast cancer related mortality. Estrogen receptor (ER) and progesterone receptor (PR) positivity were associated with increased SCGB3A1 methylation among pre- and post-menopausal cases. Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1-19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4-39.9; Stage III/IV OR = 5.6, 95% CI: 1.1-29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1-0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1-0.8; Stage III/IV OR = 0.6, 95% CI: 0.1-3.4). Among postmenopausal women, methylation of SYK was associated with increased tumor size (OR = 1.7, 95% CI: 1.0-2.7) and higher nuclear grade (OR = 2.0, 95% CI 1.2-3.6). Associations between methylation and breast cancer related mortality were observed among pre- but not post-menopausal women. Methylation of SCGB3A1 was associated with reduced risk of death from breast cancer (HR = 0.41, 95% CI: 0.17-0.99) as was BRCA1 (HR = 0.41, 95% CI: 0.16-0.97). CCND2 methylation was associated with increased risk of breast cancer mortality (HR = 3.4, 95% CI: 1.1-10.5). We observed differences in methylation associated with tumor characteristics; methylation of these genes was also associated with breast cancer survival among premenopausal cases. Understanding of the associations of DNA methylation with other clinicopathological features may have implications for prevention and treatment.
authors.affiliation: a Department of Epidemiology and Environmental Health , School of Public Health and Health Professions, University at Buffalo , Buffalo , NY , USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Callahan
authors.affiliation: a Department of Epidemiology and Environmental Health , School of Public Health and Health Professions, University at Buffalo , Buffalo , NY , USA.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Division of Cancer Prevention and Control , College of Medicine and The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.|c Department of Biochemistry and Pharmacology , University of Medicine and Pharmacy Timisoara , Timisoara , Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.affiliation: b Division of Cancer Prevention and Control , College of Medicine and The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Weng
authors.affiliation: d Department of Biostatistics and Bioinformatics , Roswell Park Cancer Institute , Buffalo , NY , USA.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: e Department of Biostatistics and Epidemiology , University of North Texas Health Science Center , Fort Worth , TX , USA.
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Tao
authors.affiliation: f Department of Cancer Prevention and Control , Roswell Park Cancer Institute , Buffalo , NY , USA.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.affiliation: a Department of Epidemiology and Environmental Health , School of Public Health and Health Professions, University at Buffalo , Buffalo , NY , USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: g City College of New York , New York , NY , USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trevisan
authors.affiliation: h Department of Cancer Genetics , Roswell Park Cancer Institute , Buffalo , NY , USA.
authors.forename: Dominic
authors.initials: D
authors.lastname: Smiraglia
authors.affiliation: i Department of Healthcare Outcomes and Policy , Roswell Park Cancer Institute , Buffalo , NY , USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Edge
authors.affiliation: b Division of Cancer Prevention and Control , College of Medicine and The Ohio State University Comprehensive Cancer Center , Columbus , OH , USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.affiliation: a Department of Epidemiology and Environmental Health , School of Public Health and Health Professions, University at Buffalo , Buffalo , NY , USA.
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics; D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D056742:Cyclin D2 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D019175:DNA Methylation; D005095:Exoribonucleases / Q000235:genetics; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009518:New York; D018168:Receptors, Retinoic Acid / Q000235:genetics; D016019:Survival Analysis; D000072377:Syk Kinase / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D048948:14-3-3 Proteins; D017766:Acid Anhydride Hydrolases; D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D056742:Cyclin D2; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D016207:Cytokines; D005095:Exoribonucleases; D051549:Glutathione S-Transferase pi; D009363:Neoplasm Proteins; D018168:Receptors, Retinoic Acid; D000072377:Syk Kinase; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C492913:BRCA1 protein, human; C080336:CCND2 protein, human; C000614131:CDKN2A protein, human; C434732:SCGB3A1 protein, human; C082925:retinoic acid receptor beta; C496556:GSTP1 protein, human; C000606896:SYK protein, human; C413442:SFN protein, human
keywords: Breast cancer; DNA methylation; breast cancer survival; tumor characteristics; tumor suppressor genes