Functional Evaluation Of BRCA1 & BRCA2 Unclassified Sequence Variants And Identification Of Critical Pathogenic Domains.
Funder
National Health and Medical Research Council
Funding Amount
$331,312.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the se ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes.Read moreRead less
The Blood Pressure Lowering Treatment Trialists' Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$166,250.00
Summary
Treatments that lower blood pressure are well known to reduce the risk of heart attack and stroke, and several different classes of blood pressure lowering drug are now widely used. While all the main classes of drug offer protection against serious complications, it is possible that one drug class may be better than the others. However, whether this is so remains uncertain and cannot be reliably determined by any one single study. The Blood Pressure Lowering Treatment Trialists' Collaboration i ....Treatments that lower blood pressure are well known to reduce the risk of heart attack and stroke, and several different classes of blood pressure lowering drug are now widely used. While all the main classes of drug offer protection against serious complications, it is possible that one drug class may be better than the others. However, whether this is so remains uncertain and cannot be reliably determined by any one single study. The Blood Pressure Lowering Treatment Trialists' Collaboration is a large international project led by a group of Australian researchers based at the Institute for International Health in Sydney. The aim of the project is to systematically gather together sufficient information from large-scale studies to make it possible to answer important outstanding questions about the effects of different classes of blood pressure lowering drugs on major outcomes, such as heart attack and stroke. The Collaboration includes many of the leading blood pressure researchers from around the world and will combine data from more than 30 trials and over 200,000 individuals. On the basis of the overview results it should be possible to provide doctors with important new information about the best blood pressure lowering treatment for their patients. A previous review of the effects of blood pressure drugs completed by the same group was published in The Lancet in 2000, and has been an important aid to many professional and regulatory groups in the year since. Reliable information about the effects of different classes of blood pressure lowering drugs is of great importance. Even if differences between the effects of different classes of drug are small, the implications for the prevention of blood pressure-related complications would be substantial because of the very large numbers of people taking them, worldwide. This collaborative overview project offers a unique opportunity to provide the most reliable and up-to-date information on the subject.Read moreRead less
This study will provide highly reliable information about the use of tight blood glucose control in critically ill patients. It involves an international collaboration between opinion leaders in this field and uses sophisticated statistical methods to combine data from all the clinical trials in this area. The study will clarify many of the current clinical questions about tight glucose control during critical illness, informing practice guidelines in Australia and around the world.
Evaluation Of Unclassified Variants Of BRCA1 And BRCA2 Using A Multifactorial Approach
Funder
National Health and Medical Research Council
Funding Amount
$456,495.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that may slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of th ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that may slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes. In addition, some of our experiments to classify variants may be useful as a screening tool to identify carriers of mutations, and so prioritize them for mutation screening.Read moreRead less
Blood Pressure Lowering In Patients With Chronic Kidney Disease: Evidence From Prospectively Planned Overview Analyses
Funder
National Health and Medical Research Council
Funding Amount
$257,271.00
Summary
This study will provide highly reliable information about the best way of managing blood pressure in people with chronic kidney disease. It will use sophisticated methods to summarize information from 25 large clinical trials and 160,000 participants to determine whether lowering blood pressure reduces the risk of heart disease and further kidney damage.The study will also determine whether currently recommended blood pressure drugs are those which will provide the most benefit.