Precision Prevention Of Colorectal Cancer: Understanding Tumourigenesis In High Risk People To Optimise Prevention
Funder
National Health and Medical Research Council
Funding Amount
$1,562,250.00
Summary
Bowel cancer, Australia’s second most common cause of cancer death, is one of the most preventable cancers. We know some people have a high risk because they carry changes in their DNA, or they have many pre-cancerous growths (polyps). Bowel cancer is increasing in young people, before 50 years of age, with no known reason. If we can identify people who have a high risk and understand how and why it develops in young Australians, we can prevent these cancers.
Identification Of Novel Colorectal Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$358,093.00
Summary
Colon cancer is one of the most common cancers, with around 1 million cases diagnosed annually. These cancers can be caused by a combination of lifestyle/environmental and genetic factors. Genetics cause ~30% of colon cancers, although the cause is unexplained in ~2/3 of these cases. The aim of this project is to discover new colon cancer genes by extensive gene sequencing of multi-case unexplained colon cancer families, and screening of additional cases and cancer-free individuals.
Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
Genomic Profiling For The Prevention Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Bowel cancer is a major health issue but is also a preventable disease. Identifying who has a high risk of developing bowel cancer from someone who has a low risk is an important way to ensure preventative medical treatment is targeted to those who are at the highest risk and will ultimately save lives. I will utilise different genomic profiling approaches to identify risk factors for bowel cancer so that they can be used to identify high risk people in the population.
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Hereditary Non-Polyposis Colorectal Cancer (HNPCC) confers a high lifetime risk of developing cancer, especially colorectal and endometrial cancer. By characterising disease presentation in the patient cohort, HNPCC in an Australian context will be better defined. The aim of this proposal is to undertake a genetic investigation such that a more comprehensive personalised patient risk-assessment can be completed by identifying genes related to disease development.
A Randomised Trial Of A Decision Aid For Women At Increased Risk For Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$115,110.00
Summary
Epithelial ovarian cancer is the leading cause of death from gynaecological malignancy in Australia. The majority of women with ovarian cancer are diagnosed with advanced disease, and the chance of cure is low. The strongest risk factor for ovarian cancer identified to date is a family history of ovarian cancer, and up to 5% of all ovarian cancers are thought to be due to dominantly inherited mutations in a small number of ovarian-cancer-related genes. National guidelines on surveillance and pro ....Epithelial ovarian cancer is the leading cause of death from gynaecological malignancy in Australia. The majority of women with ovarian cancer are diagnosed with advanced disease, and the chance of cure is low. The strongest risk factor for ovarian cancer identified to date is a family history of ovarian cancer, and up to 5% of all ovarian cancers are thought to be due to dominantly inherited mutations in a small number of ovarian-cancer-related genes. National guidelines on surveillance and prophylactic strategies have recently been ratified. These are largely based on expert opinion. Because of the uncertain efficacy of ovarian cancer screening and the high mortality associated with ovarian cancer, prophylactic oophorectomy is considered an option for women at high risk. Decisions about optimal care are difficult for both women and their doctors. Efforts to improve services for women who are trying to make informed decisions about screening and prophylactic strategies under conditions of uncertainty must be informed by sound knowledge of the efficacy of educational interventions. Decision aids have been developed as adjuncts to practitioners' counselling to prepare patients for decision-making. The proposed randomised controlled trial will compare the efficacy of a general educational pamphlet and that of a tailored decision aid. A total of 120 women at risk for ovarian cancer who are attending one of five familial cancer clinics will be included in the trial to determine the efficacy of different educational interventions in preparing women for decision-making about screening and prophylactic options.Read moreRead less
Muir Torre Syndrome: The Role Of IHC And Genotyping In Sebaceous Neoplasia To Facilitate Prevention Strategies In Colorectal And Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,786.00
Summary
Sebaceous neoplasia (SN), may be an early warning sign for Lynch syndrome (LS), an inherited cancer predisposition caused by mutations in a group of genes. There are high lifetime risks of bowel and uterine cancer, for which there are effective risk management plans if the risk is known. Clinicians are challenged by the role of SN in identifying LS. At present, it is hard to differentiate. We aim to determine features to improve the diagnosis of LS carriers.
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
Germline Epimutations Of Tumour Suppressor Genes In Familial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$502,500.00
Summary
In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called ....In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called methylation means that certain genes are spelt incorrectly or not at all. To date we have found two individuals who have this problem. Our work has shown that these individuals have inherited a genetic change and potentially could pass this change on to their offspring. This grant application seeks to formally pursue this findng. We will study a group of people in whom the genetic cause for their cancer remains unknown. Blood samples from these individuals will be examined for methylation of their DNA. A successful project will lead to a full description of this new type of hereditary cancer, and thus serve as the basis for identifying and effectively managing people and families at risk of this disease. It is likely that identification of individuals who are 'at risk' of cancer will allow us to implement preventative screening strategies. We will also be able to provide reassurance to those family members who have not inherited the methylation abnormality.Read moreRead less