domingo, 14 de julio de 2013

The ASCO Post

The ASCO Post

Epigenome-wide Study of DNA Methylation in Breast Cancer Using Prospectively Collected Samples

By Matthew Stenger
June 25, 2013, Volume 4, Issue 10

Available data suggest that DNA methylation in blood is a potential epigenetic marker of cancer risk, but this has not been evaluated on a genome-wide scale in prospective studies of breast cancer. Xu and colleagues measured DNA methylation at 27,578 CpG sites (ie, DNA regions where cytosine and guanine are separated by a single phosphate) in blood samples from 298 women who developed breast cancer 0 to 5 years after enrollment in the Sister Study cohort and in a random subgroup of 612 cohort women who remained cancer-free. Women were also genotyped for nine common polymorphisms associated with breast cancer.
A total of 250 differentially methylated CpG sites between case subjects and noncase subjects were identified. Of these, 75% were undermethylated in case subjects compared with noncase subjects. Women diagnosed within 1 year of blood sampling had small but consistently greater divergence from noncase subjects compared with women diagnosed at more than 1 year after sampling.
Receiver operating characteristic analysis estimated a prediction accuracy of 65.8% for methylation, compared with 56.0% for the Gail model and 58.8% for the common polymorphisms. The predictive accuracy of just five differentially methylated CpG sites (64.1%) was almost as high as that of the larger panel and was similar (63.1%) when replicated in a separate group of 81 women with diverse ethnic backgrounds.
The investigators concluded, “Methylation profiling of blood holds promise for breast cancer detection and risk prediction.” ■
Xu Z, et al: J Natl Cancer Inst 105:694-700, 2013.

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