Are racial disparities in colon cancer due to epigenetic outliers.

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Racial disparities in the incidence and mortality of colon cancer exist, with African Americans being the most negatively affected group. The disproportionate impact of colon cancer on African Americans could be attributed to socioeconomic, environmental and genetic factors. Our proposed study will investigate the impact of epigenetic factors, which are influenced by gene-environment interactions. Our preliminary studies have identified colon cancer patients with highly disrupted epigenomes, characterized by abnormal site-specific DNA methylation levels in normal colon mucosa. The frequency of individuals with “Outlier Methylation Phenotype” (OMP) was found to be increased in African American cancer patients compared to Caucasian cancer patients. We do not know the effect of OMP status on survival because the number of OMP patients in our preliminary study is limited. However, it is relatively easy and less invasive to get blood samples from both cancer patients and healthy individuals, so we plan to expand our preliminary study in this application. The proposed study will identify OMPs based on methylation levels in blood DNA and will determine whether African Americans colon cancer patient have a higher frequency of OMPs compared to Caucasian colon cancer patients, accounting for racial disparities in incidence and outcome. We will analyze methylation levels at ~850K CpG sites in 70 healthy and 70 colon cancer patients from each race. Furthermore, the impact of OMP status on survival and epigenetic aging, using race-specific epigenetic clocks will also be evaluated. The latter will enable us to study whether or not age-related CpGs are more disrupted in OMPs compared to non-OMPs. We anticipate that our study will provide evidence of an epigenetic basis for racial disparities in colon cancer.