TY - JOUR
T1 - Alcohol consumption in relation to aberrant DNA methylation in breast tumors
AU - Tao, Meng Hua
AU - Marian, Catalin
AU - Shields, Peter G.
AU - Nie, Jing
AU - McCann, Susan E.
AU - Millen, Amy
AU - Ambrosone, Christine
AU - Hutson, Alan
AU - Edge, Stephen B.
AU - Krishnan, Shiva S.
AU - Xie, Bin
AU - Winston, Janet
AU - Vito, Dominica
AU - Russell, Marcia
AU - Nochajski, Thomas H.
AU - Trevisan, Maurizio
AU - Freudenheim, Jo L.
N1 - Funding Information:
This study would not have been possible without the support of all the study participants and the research staff of the Western New York Exposures and Breast Cancer Study. This work was supported in part by the National Institute on Alcohol Abuse and Alcoholism ( P50-AA09802 ), the Department of Defense ( DAMD 179616202 and DAMD 17030446 ), and the National Cancer Institute ( R01CA 092040 ).
PY - 2011/11
Y1 - 2011/11
N2 - 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-β 2 (RAR-β 2) 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-β 2 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.
AB - 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-β 2 (RAR-β 2) 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-β 2 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.
KW - Alcohol consumption
KW - Breast cancer
KW - Epidemiology
KW - Epigenetics
KW - Postmenopause
KW - Promoter methylation
UR - http://www.scopus.com/inward/record.url?scp=80053245939&partnerID=8YFLogxK
U2 - 10.1016/j.alcohol.2010.11.006
DO - 10.1016/j.alcohol.2010.11.006
M3 - Article
C2 - 21168302
AN - SCOPUS:80053245939
SN - 0741-8329
VL - 45
SP - 689
EP - 699
JO - Alcohol
JF - Alcohol
IS - 7
ER -