Transformation Potential of E2 Exposed Breast Cancer Susceptibility Gene Mutation Heterozygous Epithelial Breast Cells

Susceptibility to breast cancer is related to the combination of genetic, hormonal and multiple other environmental risk factors, such as mutations in the BRCA gene and excess exposure to exogenous estrogen, respectively. BRCA is a nuclear protein that maintains genome stability, by acting as a key player in the DNA repair complex. Recently, evidence has emerged that BRCA mutation heterozygosis itself enhances aborted DNA repair and can contribute to breast cancer initiation after exposure to irradiation. In our preliminary results on short-term lymphocyte cultures, we found additional evidence that healthy heterozygous BRCA1 and BRCA2 mutation carriers have a different response to DNA damage than do non-carriers. The main aim of our ongoing project is to identify the transcriptional modulation and transformation potential of normal BRCA1 and BRCA2 mutation heterozygous epithelial breast cells following irradiation and to examine how it is affected by exposure to estrogen. Our hypotheses will be investigated by RNA-seq and microRNA-seq in order to identify a unique molecular expression profile of the estrogen exposed cells following ionizing irradiation. Understanding the role of BRCA heterozygosity in cell response to exposure to estrogen and to irradiation may facilitate the development of more appropriate diagnostic and therapeutic strategies for these individuals.

Sex

Female

Minimum age

25 Years

Maximum age

50 Years

Inclusion Criteria:

* healthy
* premenopausal
* women
* BRCA1 mutations
* BRCA2 mutations

Exclusion Criteria:

* women with breast or ovarian cancer