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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.
Acknowledgements
This work was supported by an award from the Breast Cancer Research Foundation and NIH grants U01 CA69398, P30 CA13696 and P30 ES009089. The recruitment of girls in California was supported by a Stanford Cancer Center Development grant and NIH grant R03 CA141528. This work was also supported by the National Cancer Institute, National Institutes of Health under RFA # CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR.
Figures and Tables
Figure 1 Mean differences (and 95% CI) in global DNA methylation between girls with a family history of breast cancer compared to girls without a family history of breast cancer.
Table 1 Mean levels of WBC DNA methylation in young girls using the MethyLight and LINE1 pyrosequencing assays by participant characteristics
Table 2 MultivariableTable Footnote* age-adjusted linear regression of genomic DNA methylation