Obesity-Associated Differentially Methylated Regions in Colon Cancer.

Abstract

Obesity with adiposity is a common disorder in modern days, influenced by environmental factors such as eating and lifestyle habits and affecting the epigenetics of adipose-based gene regulations and metabolic pathways in colorectal cancer (CRC). We compared epigenetic changes of differentially methylated regions (DMR) of genes in colon tissues of 225 colon cancer cases (154 non-obese and 71 obese) and 15 healthy non-obese controls by accessing The Cancer Genome Atlas (TCGA) data. We applied machine-learning-based analytics including generalized regression (GR) as a confirmatory validation model to identify the factors that could contribute to DMRs impacting colon cancer to enhance prediction accuracy. We found that age was a significant predictor in obese cancer patients, both alone (p = 0.003) and interacting with hypomethylated DMRs of ZBTB46, a tumor suppressor gene (p = 0.008). DMRs of three additional genes: HIST1H3I (p = 0.001), an oncogene with a hypomethylated DMR in the promoter region; SRGAP2C (p = 0.006), a tumor suppressor gene with a hypermethylated DMR in the promoter region; and NFATC4 (p = 0.006), an adipocyte differentiating oncogene with a hypermethylated DMR in an intron region, are also significant predictors of cancer in obese patients, independent of age. The genes affected by these DMR could be potential novel biomarkers of colon cancer in obese patients for cancer prevention and progression.