Abstract
Abstract Alterations in DNA methylation both at specific loci and overall, have been associated with breast cancer. These alterations have primarily been observed at the tissue level, although emerging studies are evaluating white blood cell (WBC) DNA methylation. To examine whether DNA methylation change measured prospectively in a family-based cohort are associated with breast cancer risk, we measured methylation levels of two repetitive elements (LINE-1, and Sat2) and three genes in mononuclear cell DNA (BLNK, CUEDC1, and IBSP) previously identified as differentially methylated in breast cancer in a genome-wide association study. After an average of 8 years of followup, we observed 81 invasive incident breast cancers and compared their methylation levels measured with baseline bloods with the remaining 1,508 women not affected with breast cancer in the New York site of the Breast Cancer Family Registry (BCFR). We found that the overall percent methylation in CUEDC1 was statistically significantly higher in breast cancer cases than in controls (78.0% versus 76.8%, respectively, p = 0.02). In a multivariable Cox Proportional Hazards model adjusting for age at blood draw, with each 1 unit increase in CUEDC1 methylation level, the OR for breast cancer increased by 1.07 (95% Confidence Interval (CI) = 1.00-1.14). We did not find the other methylation markers to be related to risk. The area under the curve was 67.6% (95% CI = 61.4% to 73.8%) for the 5 methylation markers and Gail risk score, compared with 63.3% for the Gail score only. Our finding for CUEDC1 replicates the finding from the Sisters Study supporting that selected markers selected markers of epigenetic changes measured in WBC may be potential biomarkers of breast cancer risk. Citation Format: Hui-Chen Wu, Qiao Wang, Regina M. Santella, Mary B. Terry. DNA methylation levels in mononuclear DNA in breast cancer from the New York site of the BCFR. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3835. doi:10.1158/1538-7445.AM2015-3835
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