Genetic And Environmental Risk Factors For Colorectal Cancer: Anatomic Site Specificity
Funder
National Health and Medical Research Council
Funding Amount
$560,000.00
Summary
Cancer of the large bowel (colorectal cancer) is the second most common cancer in Australians and is becoming more common. Despite this, there is still much uncertainty about what causes some people to develop this cancer. We believe that some of this uncertainty arises because there are actually different causes of cancer for different sections of the colon and rectum. This study aims to collect information from 1000 people with colorectal cancer and 1000 people without colorectal cancer, and c ....Cancer of the large bowel (colorectal cancer) is the second most common cancer in Australians and is becoming more common. Despite this, there is still much uncertainty about what causes some people to develop this cancer. We believe that some of this uncertainty arises because there are actually different causes of cancer for different sections of the colon and rectum. This study aims to collect information from 1000 people with colorectal cancer and 1000 people without colorectal cancer, and compare various factors such as their genetic makeup, diet, AND lifestyle. We expect to find that some factors are more common in people with cancer in the upper parts of the bowel, while other factors are more common in people with cancer in the lower parts of the bowel. This kind of information can be used to design programs to prevent colorectal cancer. For example, we might advise people to exercise more or eat more fish in order to decrease their chances of developing this cancer.Read moreRead less
The Consequences Of Simulated Shift Work Exposure During Gestation On The Metabolic Health Of The Adult Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Shiftwork is associated with increased risk for preterm birth & spontaneous abortion. In an animal model simulated shiftwork exposure during pregnancy increases fat deposits & reduces glucose tolerance in the adult offspring, suggesting exposure during pregnancy has lifelong health consequences for the progeny. This project will investigate the impact of shiftwork during gestation on the metabolic health of the offspring, & determine the stage of pregnancy most susceptible.
Cardiac Effects Of Exposure To Melbourne Air Pollution Caused By The 2006/2007 Bushfires In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$59,000.00
Summary
This project investigates whether the air pollution that was caused by the 2006-2007 Victorian bushfires, had an effect on the health of people living in Melbourne. Cardiovascular effects will be studied by looking at hospital admissions, out-of-hospital heart attacks and the associated death toll. As it is the expectation that bushfires will increase in the future it is important to determine the impact this may have. This research will inform appropriate public health strategies.
Risk Factors For Chronic Respiratory Diseases In Middle Age: 36-year Follow-up Of The Tasmanian Asthma Study
Funder
National Health and Medical Research Council
Funding Amount
$358,750.00
Summary
This project will improve our understanding of the causes of chronic respiratory diseases (CRDs) in adults. CRDs are clearly a major public health problem, but there are no good data on the natural history and risk factors for these diseases. Regular follow-up through childhood to adulthood is the best method to examine these factors, but such data is lacking due to difficulties in conducting long-term studies. The Tasmanian Asthma Study (TAS), based on 8,585 Tasmanians (i.e. probands) born in 1 ....This project will improve our understanding of the causes of chronic respiratory diseases (CRDs) in adults. CRDs are clearly a major public health problem, but there are no good data on the natural history and risk factors for these diseases. Regular follow-up through childhood to adulthood is the best method to examine these factors, but such data is lacking due to difficulties in conducting long-term studies. The Tasmanian Asthma Study (TAS), based on 8,585 Tasmanians (i.e. probands) born in 1961, is one of the worlds most important resources of such information. The probands, their parents (16,267) and siblings (21,044) were first investigated for respiratory problems in 1968. Subsequently, three follow-up surveys were carried out at ages 13 (1974), 20 (1981) and 31 (1992) on either the total or sub-samples of the probands. In 1992, the children and spouses of the probands were also surveyed. Information on all respiratory problems was collected in all the follow-ups, although the main focus of the TAS to date has been asthma. The probands are now reaching the age at which all CRD as a group are beginning to inflict an increasing disease burden, which will become greater in the next two decades. Hence, TAS now provides an ideal opportunity to examine the potential risk factors and natural history of and of CRDs using data collected to date and new data collected at age 43. Also, it will provide a platform for future studies to investigate the progression of CRDs in this cohort. Hence, we propose to carry out the 36 year follow-up of this cohort focusing on CRDs. This will provide important information for preventing chronic respiratory morbidity and disability in the future, which will be original and significant not only in Australia but also internationally.Read moreRead less
Deciphering Posttranslational Codes Of The Dioxin Receptor
Funder
National Health and Medical Research Council
Funding Amount
$540,083.00
Summary
The dioxin receptor (DR) is a protein which protects human cells by binding xenobiotics, ie foreign or anti-nutritional chemicals found in food sources and the general environment. When these chemicals bind the DR, it becomes an active gene regulatory protein, turning on genes that are involved in breakdown and excretion of the xenobiotics. Recently it has been found that the DR performs other important functions which are unrelated to xenobiotic breakdown. These include blood vessel development ....The dioxin receptor (DR) is a protein which protects human cells by binding xenobiotics, ie foreign or anti-nutritional chemicals found in food sources and the general environment. When these chemicals bind the DR, it becomes an active gene regulatory protein, turning on genes that are involved in breakdown and excretion of the xenobiotics. Recently it has been found that the DR performs other important functions which are unrelated to xenobiotic breakdown. These include blood vessel development in the embryonic liver and hormone production during the estrous cycle. These observations imply that natural physiological mechanisms also exist for activating the DR, providing it with a separate code to perform these innate functions. A number of man-made chemicals, such as dioxins and PCBs, are especially good at activating the DR. However, they have chlorinated chemical structures, which are not broken down by the protective system. This creates a wide range of severe toxic responses. It has been established that toxicities result from persistent hyperactivation of the DR, but how this hyperactivation induces the toxic outcomes is not known. As the DR has roles in early development and estrogen production, this project will investigate how the DR becomes activated to perform these functions. Our initial experiments have shown that the DR can be activated by normal cell signalling systems, which induce distinct modifications (a distinct code) to the protein. We are comparing this code of modifications to those induced by xenobiotics which are able to be broken down, and dioxins which are resistant to breakdown. We hypothesise that dioxins will give an excessive code of activating modifications, resulting in uncontrolled regulation of genes used in both the developmental and xenobiotic breakdown pathways. We will explore the hypothesis that this gross loss of gene regulatory control underpins the multifarious toxicities of dioxin poisoning.Read moreRead less
Risk Factors For The Development Of NAFLD Beyond Insulin Resistence: Genetic, Developmental And Environmental Influences
Funder
National Health and Medical Research Council
Funding Amount
$662,052.00
Summary
Nonalcoholic fatty liver disease (NAFLD) is the presence of fat within the liver and is associated with obesity and diabetes. NAFLD occurs in approximately one in seven Australian adolescents and may lead to cirrhosis and endstage liver disease. This proposal aims to determine what genetic and developmental risk factors lead to NAFLD, in addition to examining the role of diet and exercise. This information will lead to better treatments for this condition.
Comprehensive Assessment Of Genetic And Environmental Risk Factors For Melanoma: A Population-based Family Study
Funder
National Health and Medical Research Council
Funding Amount
$150,679.00
Summary
Excessive sunlight can cause melanoma, a serious type of skin cancer. However, there are other factors including a person's genetic make-up that are thought to put some people at higher risk. Many 'healthy' people have small changes in their genes that might make them more likely to develop melanoma. We need to know more about these genetic factors. Our study will investigate how particular small genetic changes influence a person's likelihood of developing melanoma.
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
The Impact Of Outdoor Aeroallergen Exposure On Asthma Exacerbations In Children And Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$473,924.00
Summary
Asthma is a chronic condition usually diagnosed in childhood and an important public health concern. We do not fully understand what triggers an asthma attack, although outdoor pollen and moulds may be important. This project will establish the relative importance of pollen and moulds in triggering asthma attacks among Australian children. It will fill gaps in our knowledge of environmental triggers of asthma. Such knowledge will improve asthma management and ultimately public health.
A Population-based Family Study Of Filaggrin Mutations And Allergic Disease Risk In Australia
Funder
National Health and Medical Research Council
Funding Amount
$308,584.00
Summary
It is biologically plausible that the association of known environmental risk factors for asthma may be different for genetically susceptible individuals. Few studies have examined the interaction between genetic and environmental factors. that have not considered genetic susceptibility are estimating an average risk of asthma across all genotypes in the population which may not be relevant for a particular sub-group.