reduced or undetectable in the majority of high grade, ductal breast cancers. Only about 3–8% of all women with breast cancer carry a mutation in BRCA1 or BRCA2. BRCA1 promoter hypermethylation was present in only 13% of unselected primary breast carcinomas. However, breast cancers were found to have an average of about 100-fold increase in miR-182, compared to normal breast tissue. In breast cancer cell lines, there is an inverse correlation of BRCA1 protein levels with miR-182 expression. Thus it appears that much of the reduction or absence of BRCA1 in high grade ductal breast cancers may be due to over-expressed miR-182. In addition to miR-182, a pair of almost identical microRNAs, miR-146a and miR-146b-5p, also repress BRCA1 expression. These two microRNAs are over-expressed in triple-negative tumors and their over-expression results in BRCA1 inactivation. Thus, miR-146a and/or miR-146b-5p may also contribute to reduced expression of BRCA1 in these triple-negative breast cancers. Post-transcriptional regulation by microRNA occurs either through translational silencing of the target mRNA or through degradation of the target mRNA, via complementary binding, mostly to specific sequences in the three prime untranslated region of the target gene's mRNA. The mechanism of translational silencing or degradation of target mRNA is implemented through the RNA-induced silencing complex (RISC). DNA repair gene silencing Silencing of a DNA repair gene by hypermethylation or other epigenetic alteration appears to be a frequent step in progression to cancer. As summarized in a review, promoter hypermethylation of DNA repair gene MGMT occurs in 93% of bladder cancers, 88% of stomach cancers, 74% of thyroid cancers, 40%-90% of colorectal cancers and 50% of brain cancers. In addition, promoter hypermethylation of DNA repair genes LIG4, NEIL1, ATM, MLH1 or FANCB occurs at frequencies between 33% to 82% in one or more of head and neck cancers, non-small-cell lung cancers or non-small-cell lung cancer squamous cell carcinomas. Further, the article Werner syndrome ATP-dependent helicase indicates the DNA repair gene WRN has a promoter that is often hypermethylated in a variety of cancers, with WRN hypermethylation occurring in 11% to 38% of colorectal, head and neck, stomach, prostate, breast, thyroid, non-Hodgkin lymphoma, chondrosarcoma and osteosarcoma cancers. Such silencing likely acts similarly to a germ-line mutation in a DNA repair gene, and predisposes the cell and its descendants to progression to cancer. Another review points out that when a gene necessary for DNA repair is epigenetically silenced, DNA repair would tend