Abstract A24: BRM polymorphisms, part of a novel epigenetic mechanism, are predictive of cancer risk and clinic outcome in multiple cancer types

BRM polymorphisms lie with the promoter region of the anticancer gene and SWI/SNF catalytic subunit, Brahma (SMARCA2). These polymorphisms statistically correlate with loss of BRM expression in both cell lines and primary lung tumors and function as part of an epigenetic mechanism which underlies BRM reversible silencing. Specifically, these polymorphisms function as the binding site of at least two transcription factors (MEF2D and GATA3) and two HDACs (HDAC3 and HDAC9). These proteins form a complex which drives the reversible silencing of the BRM protein. As BRM can serve as an anticancer protein, in part because BRM and SWI/SNF is required for the normal function of TP53 and RB as well as multiple DNA repair mechanisms, the silencing of BRM potentiates cancer development in mice. As such, BRM polymorphisms are predictive of cancer risk for lung cancer (n=600), breast cancer (N=300), head/neck cancer (n=400), colon cancer (N=250) and lymphoma (N=300) with an odds ratio ranging from 1.8 to 2.3. As these polymorphisms occur more frequently in African Americans, the odds ratio (cancer risk) in African Americans for lung cancer (n=250) is higher (3.5-4.5) as compared to that observed in Caucasians (2-2.3) (N=600). Similarly, BRM polymorphisms have a higher predictive value in HPV positive head/neck cancer with an odds ratio of 3.2 compared with an odds ratio of 2.0 in HPV positive head/neck cancer. This is in part due to the fact that BRM along with the HPV E2 protein regulates...
Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: Improving Cancer Risk Prediction for Prevention and Early Detection: Poster Presentations - Proffered Abstracts Source Type: research