Predicting Breast Cancer Risk by Assaying Peripheral Blood Methylation. Addendum.

摘要

We examined the concept that individuals vary in their propensity to methylate promoter CpG islands by measuring such methylation in their peripheral blood. Individuals more prone to methylate CpG islands may be more susceptible to breast or other cancers. Scope: Our objective was to test peripheral blood for promoter methylation of selected genes known to become methylated in breast cancer using sensitive and specific quantitative assays. Major findings/ up-to-date report of the progress in terms of results and significance: We developed several powerful new methodologies based on high resolution melting for sensitive detection of DNA methylation and to genotype DNA for SNPS potentially involved in methylation. Promoter region methylation was observed in all tested blood DNA samples for CDH1 and HIC1, in the majority of DNA samples for TWIST1 and DAPK1 and in a substantial proportion of the DNA samples for MGMT, APC and RARB. MGMT methylation was associated with a single nucleotide polymorphism. No BRCA1, CDKN2A, GSTP1 or RASSF1A promoter methylation was found in this sample set. Several individuals had higher levels of methylation at several loci suggestive of a methylator phenotype. These findings will be implemented to establish case control studies to determine breast cancer risk.