DNA Promoter Hypermethylation as a Blood Based Maker for Pancreatic Cancer

Overview

The objectives of this project are to test whether alteration in DNA hypermethylation in plasma is: * a diagnostic marker for pancreatic cancer * a prognostic marker for pancreatic cancer * a marker for recurrence of pancreatic cancer * changing during the course of chronic pancreatitis, with the purpose of finding patients with high risk of developing pancreatic cancer

Pancreatic cancer (PCa) is one of the most deadly cancers with a 5-year survival rate of less than 10 %. The majority of PCa are found to be none-resectable at the time of diagnosis. Only 10 - 20% of patients are offered surgical treatment, which is the only chance of cure. The mean survival times of none-resected patients are 3 to 6 months. Despite surgical treatment many patients experience recurrence. The high overall mortality is mainly caused by difficulties in early diagnosis due to unspecific/lack of symptoms in the early stages of the disease. Patients with resectable tumors and no co-morbidity, have a 5-year survival rate up to 54 %. This indicates that early detection of the disease, which enables complete surgical resection of the tumor, is a way to improve survival. Chronic pancreatitis is one of the only known risk factors for PCa. Currently there is no valid diagnostic marker for PCa. Diagnosis requires advanced methods and several of these are invasive and entail a risk of complications. A blood-based marker for pancreatic cancer would be a major achievement and of great benefit to the patients, and may even be used in screening. During development of cancer changes in DNA arise, including DNA hypermethylation where a methyl residue is attached to the DNA. The methylation most frequently occurs in the regulatory region of the gene leading to inactivity. Some of the inactivated genes are necessary to ensure the control of cell growth. When these genes are inactivated, the cell will no longer be subject to normal control mechanisms and may eventually develop into a cancer cell. Small amounts of DNA are released into the blood and can be detected in a blood sample. The DNA changes may be tumor specific and potentially useable as a marker for PCa. In 2012 our research unit in cooperation with Department of Molecular Diagnostic, Aalborg University Hospital published an optimized method for detection of hypermethylated DNA in plasma. The method has greatly improved sensitivity. The purpose of our study is to test whether alterations in DNA hypermethylations in blood can be used as: * A diagnostic marker for pancreatic cancer. * A prognostic marker for pancreatic cancer. * A marker for recurrence. * Monitoring patients with chronic pancreatitis and detecting patients with particularly high risk of developing pancreatic cancer.

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