BRCA-1 mediated activation of NF-κβ and its pro-inflammatory network drives tumorigenesis in benign breast disease patients

Abstract

BackgroundBenign breast disease (BBD) is a broad spectrum of diseases that have been linked to an elevated risk of developing breast cancer to varying degrees. The specific relation between BBD and breast cancer is yet to be resolved. MethodsHence the present study was aimed to investigate the relationship between BRCA-1 mutation and its impact on specific tumor markers and inflammatory cytokines mRNA expression in peripheral blood samples of BBD (n = 25), breast cancer (CAB) subjects (n = 25) and compared with control subjects (n = 25) through RT-qPCR. ResultsResults showed that BRCA-1 gene polymorphism was observed in BBD patients and CAB patients. Further quantitative RT-PCR was performed to detect the relative mRNA expression of NF-κβ, P53, BCL-2, Caspase-3, COX-2, IL-1β, TNF-α, &IL-6 gene transcripts in all the samples. Results showed that the transcript levels of P53 &Caspase-3 were significantly down regulated in BRCA-1 positive CAB (p = 0.0001) followed by BRCA-1 positive BBD subjects (p = 0.0001) when compared to control subjects. Besides, mRNA expression of NF-κβ, BCL-2 COX-2, IL-1β, TNF-α, &IL-6 levels were significantly elevated in BRCA-1 positive breast cancer subjects (2.0-fold, p = 0.0001) followed by BRCA-1 positive BBD subjects (1.2-fold p = 0.001) compared to control subjects. ConclusionBRCA-1 germ line mutation plays a significant role in tumor progression and pathogenesis. Also, the link between BBD and BC are associated with impaired BRCA-1 mutation results in altered expression of tumor markers in peripheral blood leucocytes.