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Exposures in early life: associations with DNA promoter methylation in breast tumors

Published online by Cambridge University Press:  10 December 2012

M.-H. Tao*
Affiliation:
Institute for Translational Epidemiology, Mount Sinai School of Medicine, New York, NY, USA
C. Marian
Affiliation:
Ohio State University Cancer Center, The Ohio State University, Columbus, OH, USA
P. G. Shields
Affiliation:
Ohio State University Cancer Center, The Ohio State University, Columbus, OH, USA
N. Potischman
Affiliation:
Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA
J. Nie
Affiliation:
Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
S. S. Krishnan
Affiliation:
Ohio State University Cancer Center, The Ohio State University, Columbus, OH, USA
D. L. Berry
Affiliation:
Lombardi Cancer Center, Georgetown University, Washington, DC, USA
B. V. Kallakury
Affiliation:
Lombardi Cancer Center, Georgetown University, Washington, DC, USA
C. Ambrosone
Affiliation:
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
S. B. Edge
Affiliation:
Department of Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA
M. Trevisan
Affiliation:
Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA School of Biomedical Education, City College of New York, New York, NY, USA
J. Winston
Affiliation:
Potomac Hospital, Woodbridge, VA, USA
J. L. Freudenheim
Affiliation:
Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA
*
*Address for correspondence: Dr M.-H. Tao, Institute for Translational Epidemiology, Mount Sinai School of Medicine, PO BOX 1057, New York, NY 10029, USA. Email menghua.tao@mssm.edu

Abstract

There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012 

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