Dataset Information

Global DNA methylation levels in girls with and without a family history of breast cancer.

ABSTRACT: Lower levels of global DNA methylation in white blood cell (WBC) DNA have been associated with adult cancers. It is unknown whether individuals with a family history of cancer also have lower levels of global DNA methylation early in life. We examined global DNA methylation in WBC (measured in three repetitive elements, LINE1, Sat2 and Alu, by MethyLight and in LINE1 by pyrosequencing) in 51 girls ages 6-17. Compared to girls without a family history of breast cancer, methylation levels were lower for all assays in girls with a family history of breast cancer, and statistically significantly lower for Alu and LINE1 pyrosequencing. After adjusting for age, body mass index (BMI), and Tanner stage, only methylation in Alu was associated with family history of breast cancer. If these findings are replicated in larger studies, they suggest that lower levels of global WBC DNA methylation observed later in life in adults with cancer may also be present early in life in children with a family history of cancer.

SUBMITTER: Wu HC

PROVIDER: S-EPMC3052913 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Global DNA methylation levels in girls with and without a family history of breast cancer.

Wu Hui-Chen HC John Esther M EM Ferris Jennifer S JS Keegan Theresa H TH Chung Wendy K WK Andrulis Irene I Delgado-Cruzata Lissette L Kappil Maya M Gonzalez Karina K Santella Regina M RM Terry Mary Beth MB

Epigenetics 20110101 1

Lower levels of global DNA methylation in white blood cell (WBC) DNA have been associated with adult cancers. It is unknown whether individuals with a family history of cancer also have lower levels of global DNA methylation early in life. We examined global DNA methylation in WBC (measured in three repetitive elements, LINE1, Sat2 and Alu, by MethyLight and in LINE1 by pyrosequencing) in 51 girls ages 6-17. Compared to girls without a family history of breast cancer, methylation levels were low ...[more]

PMID: 20930546

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Project description:BackgroundPubertal milestones, such as onset of breast development and menstruation, play an important role in breast cancer etiology. It is unclear if these milestones are different in girls with a first- or second-degree breast cancer family history (BCFH).MethodsIn the LEGACY Girls Study (n = 1040), we examined whether three mother/guardian-reported pubertal milestones (having reached Tanner Stage 2 or higher (T2+) for breast and pubic hair development, and having started menstruation) differed by BCFH. We also examined whether associations between body size and race/ethnicity and pubertal milestones were modified by BCFH. We used mother/guardian reports as the primary measure of pubertal milestones, but also conducted sensitivity analyses using clinical Tanner measurements available for a subcohort (n = 204). We analyzed cross-sectional baseline data with logistic regression models for the entire cohort, and longitudinal data with Weibull survival models for the subcohort of girls that were aged 5-7 years at baseline (n = 258).ResultsBCFH was modestly, but not statistically significantly, associated with Breast T2+ (odds ratio (OR) = 1.36, 95% confidence interval (CI) = 0.88-2.10), with a stronger association seen in the subcohort of girls with clinical breast Tanner staging (OR = 2.20, 95% CI = 0.91-5.32). In a longitudinal analysis of girls who were aged 5-7 years at baseline, BCFH was associated with a 50% increased rate of having early breast development (hazard ratio (HR) = 1.49, 95% CI = 1.0-2.21). This association increased to twofold in girls who were not overweight at baseline (HR = 2.04, 95% CI = 1.29-3.21). BCFH was not associated with pubic hair development and post-menarche status. The median interval between onset of breast development and menarche was longer for BCFH+ than BCFH- girls (2.3 versus 1.7 years), suggesting a slower developmental tempo for BCFH+ girls. Associations between pubertal milestones and body size and race/ethnicity were similar in girls with or without a BCFH. For example, weight was positively associated with Breast T2+ in both girls with (OR = 1.06 per 1 kg, 95% CI = 1.03-1.10) and without (OR = 1.14 per 1 kg, 95% CI = 1.04-1.24) a BCFH.ConclusionsThese results suggest that BCFH may be related to earlier breast development and slower pubertal tempo independent of body size and race/ethnicity.

Dataset Information

Global DNA methylation levels in girls with and without a family history of breast cancer.

Publications

Global DNA methylation levels in girls with and without a family history of breast cancer.

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