Population-based Detection Of Hereditary Non-polyposis Colorectal Cancer: Development Of New Best Practice
Funder
National Health and Medical Research Council
Funding Amount
$356,250.00
Summary
Approximately 1-2% of all large bowel cancers are thought to be caused by inherited defects in genes involved in the repair of DNA. These cancers are indistinguishable from those that occur in the general population and this has made it difficult to identify individuals and families with the defective gene. It has been estimated that only about 10-20% of individuals affected by this familial cancer syndrome are being referred to specialized genetic service centres for testing. The large majority ....Approximately 1-2% of all large bowel cancers are thought to be caused by inherited defects in genes involved in the repair of DNA. These cancers are indistinguishable from those that occur in the general population and this has made it difficult to identify individuals and families with the defective gene. It has been estimated that only about 10-20% of individuals affected by this familial cancer syndrome are being referred to specialized genetic service centres for testing. The large majority of familial colorectal cancers occur in young patients aged less than 60 years at diagnosis. Identification of these cases would allow genetic testing to be carried out on other family members who might also carry the mutant gene, thus allowing regular surveillance and a far greater likelihood of early detection and therefore cure. The aim of this project is to use a relatively simple laboratory-based method to test for the possibility that colorectal cancer in young patients (<60 years) may be inherited. From our preliminary data we expect that about 2% of all large bowel cancers, or 20 cases per year in Western Australia, may be familial. These individuals will be referred to Genetic Services WA for proper evaluation of their family history for cancer and for further DNA testing in an attempt to identify the defective gene. For positive cases, affected family members could then be tested for the gene after appropriate genetic counselling.Read moreRead less
In Vivo Models For Understanding The Cellular And Molecular Pathogenesis Of Barrett's Oesophagus
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce th ....The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce the normal layered structure of the human oesophageal lining in the laboratory and we propose to use these models to address key issues in the biology of Barrett's oesophagus. In aim 1, we wish to determine if the cells in patients with Barrett's have been permanently, or only transiently, altered and to understand the role of gastric acid- bile and accessory cells in this transformation. In aim 2 we will look more closely at the molecular changes that drive the cellular transformation characteristic of Barrett's. We will do this by manipulating the expression of selected genes in human oesophageal cells and assessing the effects of these genes on cell growth and differentiation using our cell culture models. The results of these studies will pave the way for the design of appropriate clinical strategies to treat Barrett's oesophagus and prevent the progression of this premalignant condition to oesophageal adenocarcinoma.Read moreRead less
The CpG Island Methylator Phenotype In Colorectal Cancer - Pathways And Precursors
Funder
National Health and Medical Research Council
Funding Amount
$517,272.00
Summary
Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four differen ....Bowel cancer is one of the most common cancers affecting Australians. It will affect 1-23 Australians and is a leading cause of cancer-related death. If diagnosed early, bowel cancer is curable with surgery. Unfortunately, symptoms are often not present until the cancer is advanced, when the cure rate is only 55%. It has been recognised that there are different types of bowel cancer depending on different genes which can be inactivated abnormally. We propose that there are at least four different subgroups of bowel tumours, and that each of these may have different physical properties and responses to therapy. We aim to better characterise these subgroups to increase our understanding of how normal bowel can change into a small polyp, that may grow into a cancer. Understanding the gene changes leading to each subtype of bowel cancer will in the future allow the development gene markers for early detection as well as the possibility of individualised patient therapy. We are also studying tiny biopsies of normal bowel tissue from patients either with or without polyps, to try to understand the very earliest changes which may underly the development of a bowel polyp.Read moreRead less