PO-503 The cohesin stromal antigen 1 (SA-1) modulates colonic and colorectal cancer (CRC) stem cells: mechanism for racial disparities

Introduction CRC disproportionately impacts African-Americans (incidence and mortality increased by ~25% and~50%, respectively). While mechanisms remain unclear, Vogelstein posited that the number of stem cell divisions determine CRC risk Science 2015. CRC stem cells may impact mortality via chemoresistance. LGR5, aldehyde dehydrogenase (ALDH1a3) and DCAMKL1 are markers of both intestinal and CRC stem cells. We have noted loss of SA-1 (a chromatin remodeler) occurred during colonic field carcinogenesis was markedly accentuated in Blacks ( Cancer Prev Res 2016) via specific SNPs ( Neoplasia 2018). SA-1 loss was also associated with poorer CRC prognosis. We hypothesised that SA-1 loss leads to stem cell induction and hence CRC disparities. Material and methods Rectal biopsies were obtained from endoscopically normal mucosa from ~200 patients undergoing screening colonoscopy with an IRB approved protocol. SA-1 was assessed by RT-PCR normalised to β-actin. We modulated SA-1 in human CRC cell line HT29 and tested efficacy of chemotherapy 5 fluorouracil (5-FU) and oxaliplatin via annexin V apoptosis assay. Results and discussions Adenoma-harbouring subjects had ~50% increase in LGR5, ALD1a3 and DCAMKL1 (p Conclusion This novel finding that the proneoplastic effects of SA-1 loss may be transduced through intestinal/colonic stem cell (CRC incidence) and also augmenting CRC stem cells resulting in chemotherapy resistance (CRC mortality). Future studies may mitigate CRC disparities in Blacks through development of effective biomarkers and therapeutic.