title: Exposures in early life: associations with DNA promoter methylation in breast tumors.
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.
authors: 1 Institute for Translational Epidemiology, Mount Sinai School of Medicine, New York, NY, USA.
authors: M-H
authors: MH
authors: Tao
authors: 2 Ohio State University Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: C
authors: C
authors: Marian
authors: 2 Ohio State University Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: P G
authors: PG
authors: Shields
authors: 3 Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA.
authors: N
authors: N
authors: Potischman
authors: 4 Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
authors: J
authors: J
authors: Nie
authors: 2 Ohio State University Cancer Center, The Ohio State University, Columbus, OH, USA.
authors: S S
authors: SS
authors: Krishnan
authors: 5 Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors: D L
authors: DL
authors: Berry
authors: 5 Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
authors: B V
authors: BV
authors: Kallakury
authors: 6 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: C
authors: C
authors: Ambrosone
authors: 7 Department of Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: S B
authors: SB
authors: Edge
authors: 4 Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
authors: M
authors: M
authors: Trevisan
authors: 9 Potomac Hospital, Woodbridge, VA, USA.
authors: J
authors: J
authors: Winston
authors: 4 Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA.
authors: J L
authors: JL
authors: Freudenheim