Genome-Wide DNA Methylation Markers for Predicting the Risk of Liver Cancer in Non- Alcoholic Fatty Livers
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The Mexican American population in south Texas exhibits a disproportionately high number of liver cancer due to a high prevalence of non-alcoholic fatty liver disease (NAFLD), which affects 1 in 5 adults in Texas and 1 in 3 of its Hispanic population. The existence of a large population in Texas at risk for liver cancer provides an opportunity to develop and implement risk mitigation and disease prevention strategies that will have a major impact on the health of Texans. There is a large unmet need for tools that can be used to determine the risk of NAFLD individuals in developing cancer. Our objective is to identify DNA modification (called 'methylation') markers that can predict the develo... Read More The Mexican American population in south Texas exhibits a disproportionately high number of liver cancer due to a high prevalence of non-alcoholic fatty liver disease (NAFLD), which affects 1 in 5 adults in Texas and 1 in 3 of its Hispanic population. The existence of a large population in Texas at risk for liver cancer provides an opportunity to develop and implement risk mitigation and disease prevention strategies that will have a major impact on the health of Texans. There is a large unmet need for tools that can be used to determine the risk of NAFLD individuals in developing cancer. Our objective is to identify DNA modification (called 'methylation') markers that can predict the development of liver cancer in a mouse model and then use the mouse markers to identify their human counterparts. This proposal has two specific aims. Aim 1 will identify differentially methylated DNA regions that distinguish cancer-sensitive vs. resistant fatty livers in the mouse model. Aim 2 will identify human prognostic markers based on the mouse markers. Upon completion, we will have identified new diagnostic markers that can predict the risk of metabolic liver cancer in the NAFLD population early enough when prevention and intervention can be more easily and effectively implemented. This outcome will have a major impact on the health of Texans by developing a new tool to profile the Texas NAFLD population and determine their risk of developing liver cancer, setting up an implementation platform for early cancer prevention, using this prognostic tool to evaluate the cause and improve environmental health conditions, and providing scientific support to the therapeutic use of epigenetic modifiers to prevent the occurrence of metabolic liver cancer and/or reverse its progression. This proposal may eventually lead to the reversal of the rising trajectory of liver cancer incidence and mortality, as well as the resolution of the liver cancer-related health disparity issue in Texas
