Measuring constitutional BRCA1 methylation: a future tool for risk assessment

Up to now the emphasis has been on identifying individuals with a family history of breast cancer. Our approach to understanding non-familial breast cancer risk is based on the emerging field of epigenetics which is the study of how our genetic machinery is programmed.

Mutations in the BRCA1 gene, which is involved in the repair of DNA damage, underlie much of familial breast and ovarian cancer. Our previous studies indicate that the epigenetic modification called DNA methylation, which can inactivate the BRCA1 gene, might be a novel mechanism of breast cancer predisposition. DNA methylation of the BRCA1 gene is known to occur in breast cancer (and was first reported by us) but it has been unclear as to how much this DNA methylation might be an initiating event in the cancer.

The novelty of our approach is to examine normal tissues for evidence of DNA methylation of the BRCA1 cancer gene to identify individuals that may be at increased risk of developing breast cancer. Using very sensitive methodologies developed by us, it was shown that BRCA1 methylation in the normal tissues was much more common in some breast cancer patients.

Studies of methylation as a mechanism of cancer predisposition represent a frontier area in cancer research. Once it is understood how such methylation arises, it may be possible to for dietary or other environmental interventions to reduce this methylation, and thereby decrease the risk of developing cancer.