Effect of fructose on human colon DNA methylation: implication for racial disparities in colorectal cancer risk

"Background: An increasing body of evidence has linked fructose intake to colorectal cancer (CRC). African Americans (AAs) consume greater quantities of fructose and are more likely to develop right-side colon cancer than European Americans.Objective: We examined the hypothesis that fructose consumption leads to genomic differences associated with CRC tumor biology.Methods: DNA methylation data from this study was obtained using the Illumina Infinium MethylationEPIC kit (GSE151732). Right and left colon differentially methylated regions (DMRs) were identified using DMRcate through analysis of fructose consumption in normal AA colon biopsies (n=79) undergoing screening colonoscopy. Secondary analysis of CRC tumors was carried out using data derived from TCGA-COAD, GSE101764 and GSE193535. Right colon organoids derived from AA normal colon tissues were exposed to 4.4mM of fructose for 72 hours. Fructose-associated differentially expressed genes (DEGs) were identified using DESeq2. This package was also used to identify DEGs in CRC tumors from TCGA-COAD.Results: We identified 4,263 right colon fructose-associated DMRs (FDRConclusions: Our data support that dietary fructose exerts a greater CRC risk-related effect in right than left colon among AAs, alluding to its potential role in contributing to racial disparities in CRC."