Slc5a8 gene, a transporter of butyrate: A gut flora metabolite, is frequently methylated in african american colon adenomas

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Abstract

BACKGROUND: Colon cancer is one of the leading causes of cancer related deaths. Its impact on African Americans (AAs) is higher than in the general population both in the incidence and mortality from the disease. Colon cancer aggressiveness in AAs as well as non-frequent check-ups and follow up in this population have been proposed as ways to explain the observed discrepancies. These facts made the detection of early carcinogenesis markers in this population a priority. MATERIALS AND METHODS: Here, we analyzed 50 colon adenomas from AA patients for both microsatellite instability (MSI) and the methylation status of SLC5A8 gene. This gene's product is involved in the transport of butyrate that has anti-proliferative properties through its effects on histone acetylation and gene expression. A proteomic analysis to check the expressed histones in adenoma and normal tissues was also performed. RESULTS: The analyzed samples displayed 82% (n = 41) methylation level of SLC5A8 gene in adenomas. The MSI-H (high) adenoma were about 18% (n = 9) while the rest were mostly MSS (microsatellite stable) with few MSI-L (Low). No association was found between SLC5A8 methylation and the MSI status. Also, there was no association between SLC5A8 methylation and the sex and age of the patients. However, there were more right sided adenomas with SLC5A8 methylation than the left sided ones. The proteomic analysis revealed distinct histone expression profiles between normal and adenoma tissues. CONCLUSION: SLC5A8 is highly methylated in AA colon adenomas which points to its potential use as a marker for early detection. The MSI rate is similar to that found in colon cancer tumors in AAs. These findings suggest that both processes stem from the same epigenetic and genetic events occurring at an early stage in colon carcinogenesis in AAs.

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Brim, H., Kumar, K., Nazarian, J., Hathout, Y., Jafarian, A., Lee, E., … Ashktorab, H. (2011). Slc5a8 gene, a transporter of butyrate: A gut flora metabolite, is frequently methylated in african american colon adenomas. PLoS ONE, 6(6). https://doi.org/10.1371/journal.pone.0020216

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