Alexandra J White1, Dale P Sandler2, Sophia C E Bolick3, Zongli Xu2, Jack A Taylor4, Lisa A DeRoo5. 1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC 27599, United States. 2. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States. 3. Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States. 4. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States; Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States. 5. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States. Electronic address: DeRooL@niehs.nih.gov.
Abstract
BACKGROUND: DNA methylation patterns are heritable but can change over time and in response to exposures. Lower global DNA methylation, which may result in increased genomic and chromosomal instability, has been associated with increased cancer risk. Physical activity is a modifiable factor that has been inversely related to the risk of cancer. Changes in DNA methylation may be a mechanism by which lifestyle and environment factors influence disease. We investigated the relationship between DNA methylation and physical activity in a sample of women enroled in The Sister Study, a large United States (U.S.) cohort study of women aged 35-74 years with a family history of breast cancer. METHODS: Global DNA methylation was measured using bisulphite-converted DNA and pyrosequencing of a LINE-1 repetitive sequence in the peripheral blood of 647 non-Hispanic white women. Physical activity (average hours per week) was retrospectively assessed for three time periods: childhood (ages 5-12), teenage years (ages 13-19) and the previous 12 months. FINDINGS: Compared with women with physical activity levels below the median for all three time periods, those at or above the median physical activity for one (β = 0.20, 95% confidence interval (CI): -0.10, 0.49), two (β = 0.22, 95% CI: -0.08, 0.52) or all three (β = 0.33, 95% CI: 0.01, 0.66) time periods had increased global methylation. INTERPRETATION: Maintaining higher levels of physical activity over these three time periods was associated with increased global DNA methylation, consistent with reported associations between exercise and decreased cancer risk. Published by Elsevier Ltd.
BACKGROUND: DNA methylation patterns are heritable but can change over time and in response to exposures. Lower global DNA methylation, which may result in increased genomic and chromosomal instability, has been associated with increased cancer risk. Physical activity is a modifiable factor that has been inversely related to the risk of cancer. Changes in DNA methylation may be a mechanism by which lifestyle and environment factors influence disease. We investigated the relationship between DNA methylation and physical activity in a sample of women enroled in The Sister Study, a large United States (U.S.) cohort study of women aged 35-74 years with a family history of breast cancer. METHODS: Global DNA methylation was measured using bisulphite-converted DNA and pyrosequencing of a LINE-1 repetitive sequence in the peripheral blood of 647 non-Hispanic white women. Physical activity (average hours per week) was retrospectively assessed for three time periods: childhood (ages 5-12), teenage years (ages 13-19) and the previous 12 months. FINDINGS: Compared with women with physical activity levels below the median for all three time periods, those at or above the median physical activity for one (β = 0.20, 95% confidence interval (CI): -0.10, 0.49), two (β = 0.22, 95% CI: -0.08, 0.52) or all three (β = 0.33, 95% CI: 0.01, 0.66) time periods had increased global methylation. INTERPRETATION: Maintaining higher levels of physical activity over these three time periods was associated with increased global DNA methylation, consistent with reported associations between exercise and decreased cancer risk. Published by Elsevier Ltd.
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