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Prostate cancer (CaP) is one of the most common cancers in men and causes more than 500 deaths every year in Ireland. It mainly affects men over the age of 65 and with an ageing population, figures worldwide are increasing. Treatment is potentially curative when the disease is found early. The challenge is to distinguish the 'tigers' from the 'pussy-cats', to diagnose early those CaPs that are likely to spread rapidly and kill the patient if left untreated. CaP is caused by a range of factors, including abnormal growth of prostate cells. Every cell in our body contains instructions (genes contained in DNA) telling the cell how it works. Methylation is a chemical alteration of DNA that switches off genes that control normal cellular processes. Abnormally high levels of methylation occur in CaP, inactivating many important genes. Recently, a new target of methylation has been discovered, miRNA genes. MiRNAs themselves turn off of a wide range of genes and particular miRNAs can be detected in different cancers. This study will investigate how methylation can be used as an early warning-system to detect aggressive CaP and to distinguish between low-risk and high-risk disease. We will first identify miRNAs that are methylated in CaP. Next, we will combine these miRNAs with our previously identified methylated genes to generate a CaP methylation signature, which will test in samples of blood, urine and prostate tissue, collected from CaP patients.
The aim of this study is to identify a number of markers which can be used to detect aggressive forms of prostate cancer and to distinguish between low-risk and high risk disease. A number of specific DNA modifications will be examined as potential markers of aggressive disease. These DNA modification markers will subsequently be combined with additional genetic markers, called miRNAs, to ultimately develop a panel of predictive markers which can be used for the detection of aggressive forms of prostate cancer in patients.
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