View clinical trials related to Aberrant DNA Methylation.Filter by:
Colorectal cancer (CRC) is one of the most common forms of cancer and the second leading cause of cancer-related deaths in the western world. CRC mortality is related to stage of disease with a five year survival for early-stage disease of 77.0% and 50.8% for late stage disease. Methods for early detection of primary as well as recurrent CRC are therefore important to increase patient survival. Tumour biomarkers from blood, stool, or urine could aid the early diagnostics of CRC, but despite extensive research such markers have only provided limited clinical value. Sporadic CRC develops as a result of the accumulation of genetic and epigenetic alterations. Epigenetic alterations include DNA hypermethylation, which through transcriptional silencing of tumour suppressor genes is associated with cancer development and cancer progression. The search for gene promoter regions hypermethylated in cancer has been ongoing for nearly two decades, and a number of genes have been shown to be preferentially hypermethylated in CRC. Therefore, hypermethylated DNA in plasma has been suggested as a marker for tumour-stage and survival in CRC patients. The only approved biomarker for the detection of CRC recurrence is the protein carcinoembryonic antigen (CEA). CEA is limited by its low sensitivity and therefore not recommended as a diagnostic biomarker. Hypermethylation of CRC specific genes as part of a molecular biomarker panel measured in blood could prove to be a recurrence marker in CRC patients, with elevated sensitivity and specificity. The aims of this project are to examine if hypermethylation of specific genes measured from cell-free DNA in plasma of CRC patients can be used to detect primary CRC, to detect CRC recurrence and to be a biomarker for CRC prognosis. Development of a reliable sensitive and specific biomarker for CRC will immensely improve the diagnostics and handling of CRC patients.
Accumulating evidence suggests that early-life nutrition can affect metabolism and thus increase the risk of disease in adulthood (e.g. type II diabetes and obesity). One possible mechanism to explain these effects is epigenetic variation at critical periods of development. Epigenetic variation describes non-inherited permanent alterations to an individuals DNA. Recent work in mouse models has demonstrated that maternal nutritional status can affect such epigenetic processes such as DNA methylation and gene expression during embryonic development, with profound effects on outcomes. The investigators aim to study these processes in humans for the first time. The investigators will exploit the "experiment of nature" setting in The Gambia, i.e. fluctuation in diet according to season. During the 'hungry' season diets are known to be depleted in nutrients required for epigenetic gene regulation. Nutritional biomarkers in blood as well as the dietary intake will be measured in pregnant women according to season. A blood sample will also be taken from babies born to these women to determine whether there is a direct effect of diet on mothers' nutritional status and hence variation in DNA methylation patterns in their babies by season.