The BRCA1 tumor suppressor: potential long-range interactions of the BRCA1 promoter and the risk of breast cancer

Abstract

Breast cancer is a complex disease with different phenotypes associated with genetic and non-genetic risk factors. An aberrant expression of the BRCA1 tumor suppressor as well as dysfunction of BRCA1 protein caused by germline mutations are implicated in breast cancer aethiology. BRCA1 plays a crucial role in genome and epigenome stability. Its expression is auto regulated and modulated by various cellular signals including metabolic status, hypoxia, DNA damage, estrogen stimulation. The review describes breast cancer risk factors, the BRCA1 gene expression and functions as well as covers the role of long-range genomic interactions, which emerge as regulators of gene expression and moderators of genomic communication. The potential long-range interactions of the BRCA1 promoter (driven by polymorphic variant rs11655505 C/T, as an example) and their possible impact on the BRCA1 gene regulation and breast cancer risk are also discussed.