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.