View Full Version : Blood test can predict risk of developing breast cancer

Jean M
06-28-2014, 08:50 AM
Shahzia Anjum et al., A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival, Genome Medicine 2014, 6:47. Online 27 June 2014 ahead of print. http://genomemedicine.com/content/6/6/47/abstract


BRCA1 mutation carriers have an 85% risk of developing breast cancer but the risk of developing non-hereditary breast cancer is difficult to assess. Our objective is to test whether a DNA methylation (DNAme) signature derived from BRCA1 mutation carriers is able to predict non-hereditary breast cancer.

In a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type controls) blood cell DNA samples were profiled on the Illumina 27 k methylation array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme signature was derived and tested in two cohorts: (i) The NSHD (19 breast cancers developed within 12 years after sample donation and 77 controls) and (ii) the UKCTOCS trial (119 estrogen receptor positive breast cancers developed within 5 years after sample donation and 122 controls).

We found that our blood based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the NSHD resulted in a Receiver Operating Characteristics (ROC) Area Under the Curve (AUC) of 0.65 (95% CI 0.51-0.78, P = 0.02) which did not validate in buccal cells from the same individuals. Applying the signature in blood DNA from UKCTOCS volunteers resulted in AUC of 0.57 (95% CI 0.50-0.64; P = 0.03) and is independent of family history or any other known risk factors. Importantly the BRCA1- mutation DNAme signature was able to predict breast cancer mortality (AUC = 0.67; 95% CI 0.51-0.83) P = 0.02). We also found that the 1074 CpGs which are hypermethylated in BRCA1 mutation carriers are massively enriched for stem cell polycomb group target genes (P < 10−20).

I'm thrilled by this paper, not just for the very useful finding, but because they may have used my blood sample. I participated in the UKCTOCS trial.