Germline Mutations In Mismatch Repair Genes: Prevalence, Risk Of Cancer, And Environmental Modifiers Of Risk.
Funder
National Health and Medical Research Council
Funding Amount
$216,750.00
Summary
Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their ....Aims: 1. Develop a model that will predict who has a mutation in a group of genes that cause cancer 2. Estimate risk of cancer in people who have a mutation in these genes (carriers) 3. Determine if cancer risk in carriers can be reduced People who inherit a mutation in a group of genes called 'mismatch repair genes' are at increased risk of cancer, particularly cancer of the colon and rectum. If these carriers can be identified they can take preventive measures such as screening to reduce their risk of cancer and death. We will develop a model using data from the Colon Cancer Family Registry (CFR), the world's largest dataset of carriers and non-carriers which has already recruited and genetically tested over 4,000 families from Australasia, USA and Canada. The model will allow clinicians to predict who is a likely be a carrier based so they can be tested for the mutation. We know the risk of cancer is high in carriers, but we don't have precise estimates. We will use the Colon CFR applying sophisticated statistical methods required to answer this question. This data is critical for genetic counselling so appropriate decisions can be made by the patient and the doctor as to what preventive measures to take. We will also use the Colon CFR data to find out what how the carriers who develop cancer differ from those who stay cancer free using their completed lifestyle questionnaires which includes questions on diet, smoking, alcohol consumption, exercise, aspirin use, and oral contraceptive pill use. We may identify risk factors that carriers can avoid (or take up if they reduce cancer risk) to reduce their risk of cancer.Read moreRead less
Environmental Risk Factors For Iron Overload-related Disease In A Cohort Study Of Hereditary Haemochromatosis
Funder
National Health and Medical Research Council
Funding Amount
$152,936.00
Summary
Results published last year from our Melbourne HealthIron study of hereditary haemochromatosis (iron overload disease) show that almost one third of the 50,000 men genetically at risk of iron overload in Australia will develop symptoms of disease including fatigue, arthritis and liver damage. We will use data from the recent follow-up of the Health2020 cohort, of which HealthIron is a sub-study, to determine environmental risk factors for progression to disease in people with iron overload.
Predicting The Individual Risk Of Prostate Cancer In Australian Men
Funder
National Health and Medical Research Council
Funding Amount
$348,656.00
Summary
Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently a ....Prostate cancer is a major cause of disability and death in Australian men. A number of factors, particularly age and family history, influence the risk of prostate cancer but, in contrast to breast cancer, we don't know what is the risk of developing prostate cancer over a period of time for a man with a specific set of risk factors. In fact, while a number of statistical models have been developed that use a woman's risk factor profile to estimate her risk of breast cancer, none is currently available for prostate cancer. We will apply standard statistical methods to existing data from the Australian Risk Factors for Prostate Cancer study and from the Australian Institute of Health and Welfare to develop a prostate cancer risk prediction model. We will test how factor like age, detailed family history, diet, baldness status and possibly previous PSA tests and prostate biopsies predict the risk. After developing the model, we will test the accuracy of the predictions in three ways. First, using existing data from the Australian Prostate Cancer Family Study, we will see whether the number of cases in a group of men is close to the number predicted by the model (calibration). Second, to test whether the model discriminate well men who develop prostate cancer from those who do not, we will collect family trees in a sample from the Melbourne Collaborative Cohort Study. We will use these data also to estimate the optimal cut point: men above this level of risk will be considered at high risk. Third, we will apply the model to existing data from the Dutch Prostate Cancer Family Study (DPCFS) to test whether the optimal cut point identify high-risk men and to validate the model in a non-Australian population. Finally, we will prepare a computer package that health professionals will use as decision-making tool in different scenarios including individual cancer risk assessment, design of prevention trials and targeting prevention programs to high-risk men.Read moreRead less
Genetic Epidemiology Of Endometrial Cancer: Towards Understanding Aetiology And Improving Risk Prediction.
Funder
National Health and Medical Research Council
Funding Amount
$353,573.00
Summary
Studies investigating thousands of genetic markers have revolutionised our understanding of genes involved in cancer, and shown that a single gene can be associated with multiple cancers. We will conduct the largest ever study to find new genes for endometrial cancer, the most common gynaecological cancer. Our unique approach will examine >11million markers across the genome, some specifically in regions known to be important for other cancers. Findings will be used for risk prediction models ....Studies investigating thousands of genetic markers have revolutionised our understanding of genes involved in cancer, and shown that a single gene can be associated with multiple cancers. We will conduct the largest ever study to find new genes for endometrial cancer, the most common gynaecological cancer. Our unique approach will examine >11million markers across the genome, some specifically in regions known to be important for other cancers. Findings will be used for risk prediction models.Read moreRead less
Clinical, Environmental And Genetic Factors And The Risk Of Oesophageal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$145,685.00
Summary
Oesophageal cancer is a rapidly fatal disease which is becoming more common in Australia, the United States and other industrialised nations. This study will examine the mechanisms leading to the development of oesophageal cancer and aims to measure the effects of genes and environment on the burden of cancer. Ultimately, this research will help target persons at highest risk so that screening, prevention and surveillance efforts can be directed more effectively.
Obesity, Pre-diabetes And Future Risk Of Diabetes: Maximising The Evidence, Minimising The Cost
Funder
National Health and Medical Research Council
Funding Amount
$470,136.00
Summary
The overarching aim of this proposal is to reliably determine how best to identify people at high risk of developing future diabetes. We will do this by using information on biological and behavioural risk factors that was collected on nearly 200,000 people many years ago and who were subsequently followed up to see who developed diabetes. This information will be used to create a risk prediction tool for spotting individuals most at risk of developing diabetes at some point in the future.
Automated Mammographic Measures That Predict Breast Cancer Risk
Funder
National Health and Medical Research Council
Funding Amount
$406,260.00
Summary
Mammographic density (MD) is one of the strongest predictors of breast cancer risk but its impractical measurement prevents its use in a clinical setting. An automated measure of MD would allow screening programs to identify and target women at higher risk of breast cancer which could lead to earlier diagnoses and better breast cancer outcomes. We aim to develop an automated measurement, maximized by its ability to predict breast cancer risk, and applicable to both film and digital mammograms.
Monitoring cardiovascular risk is a major part of the clinical workload both in general practice and specialty areas, but it is an under-researched area, reflected in a general lack of evidence based guidelines. My research will evaluate how to optimise the monitoring of cardiovascular risk both before and after starting treatment. By maximising clinical benefits for patients and minimising unnecessary resource use, my research will benefit patients, clinicians and the community at large.
Novel Genetic And Environmental Modifiers Of The Risk Of Iron Overload-related Disease In HFE-associated Hereditary Haemochromatosis In Cohort Of Middle-aged Australians
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
People who carry mutations in the HFE gene are pre-disposed to body iron overload but not all of them developed subsequent disease. According to the investigators of the “HealthIron” study in Melbourne, only 28% of men and 1% of women with faulty HFE genes go on to develop disease. This study has recruited more than 1,000 people from the community, and will determine which environmental and genetic risk factors stop people with iron overload from getting symptoms of disease.
Dengue Transmission Under Climate Change In Northern Australia: Linking Ecological And Population Based Models To Develop Adaptive Strategies
Funder
National Health and Medical Research Council
Funding Amount
$444,293.00
Summary
The mosquito-transmitted viral disease, dengue, is likely to be influenced by climate change. It has been accorded priority for human health adaptation research (National Adaptation Research Plan, Human Health). Dengue has major health impacts in North Queensland, and causes major losses to the Queensland blood supply. The research will develop a model for climate-related changes in the future occurrence of dengue to predict risk in North Queensland and other parts of Australia.