title: Alcohol consumption in relation to aberrant DNA methylation in breast tumors.
abstract: The mechanism for the observed association of alcohol consumption breast cancer risk is not known; understanding that mechanism could improve understanding of breast carcinogenesis and optimize prevention strategies. Alcohol may impact breast malignancies or tumor progression by altering DNA methylation. We examined promoter methylation of three genes, the E-cadherin, p16, and retinoic acid-binding receptor-β2 (RAR-β2) genes in archived breast tumor tissues from participants in a population-based case-control study. Real time methylation-specific PCR was performed on 803 paraffin-embedded samples, and lifetime alcohol consumption was queried. Unordered polytomous and unconditional logistic regression were used to derive adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RAR-β2 methylation was not associated with drinking. Among premenopausal women, alcohol consumption was also not associated with promoter methylation for E-cadherin and p16 genes. In case-case comparisons of postmenopausal breast cancer, compared with lifetime never drinkers, promoter methylation likelihood was increased for higher alcohol intake for E-cadherin (OR=2.39; 95% CI, 1.15-4.96), in particular for those with estrogen receptor-negative tumors (OR=4.13; 95% CI, 1.16-14.72), and decreased for p16 (OR=0.52; 95% CI, 0.29-0.92). There were indications that the association with p16 was stronger for drinking at younger ages. Methylation was also associated with drinking intensity independent of total consumption for both genes. We found alcohol consumption was associated with DNA methylation in postmenopausal breast tumors, suggesting that the association of alcohol and breast cancer may be related, at least in part, to altered methylation, and may differ by drinking pattern.
authors.affiliation: Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA. menghua.tao@mssm.edu
authors.forename: Meng Hua
authors.initials: MH
authors.lastname: Tao
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Susan E
authors.initials: SE
authors.lastname: McCann
authors.forename: Amy
authors.initials: A
authors.lastname: Millen
authors.forename: Christine
authors.initials: C
authors.lastname: Ambrosone
authors.forename: Alan
authors.initials: A
authors.lastname: Hutson
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Edge
authors.forename: Shiva S
authors.initials: SS
authors.lastname: Krishnan
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.forename: Janet
authors.initials: J
authors.lastname: Winston
authors.forename: Dominica
authors.initials: D
authors.lastname: Vito
authors.forename: Marcia
authors.initials: M
authors.lastname: Russell
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Nochajski
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trevisan
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D011401:Promoter Regions, Genetic / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics
chemical_list: D015820:Cadherins; D018168:Receptors, Retinoic Acid