Statistical Analyses Of Breast Cancer Risks For Australian BRCA1 And BRCA2 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$424,628.00
Summary
About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. ....About 10 years ago two genes, called BRCA1 and BRCA2, were discovered. The normal function of these genes is to prevent breast and other cancers from developing. All people have two copies of each gene, one inherited from their mother and one from their father. Women who have inherited a fault in one copy are at increased risk of breast and ovarian cancer. There has been considerable controversy about what their actual cancer risks are, especially about how those risks might depend on their age. We have already conducted studies on this and have developed the necessary statistical methods to address these issues by analysing data from the families in which there are faulty genes. In this study we propose to use two large Australian studies, one of families with multiple-cases of breast cancer (Kathleen Cuningham Consortium for Research on Familial Breast Cancer; kConFab) and the other of the families of women with breast cancer chosen, irrespective of their family cancer histories, through the Victorian and NSW Cancer Registries (Australian Breast Cancer Family Study; ABCFS). A large amount of work has already been conducted to identify these families and test them for faults in BRCA1 and BRCA2. There are over 350 families who carry faults, making this one of the largest studies of its type in the world. We will check the cancer histories of these families and determine which members have, or are likely to have, inherited a faulty gene. We will then estimate the breast and ovarian cancer risks accurately, and with much more precision, than has been done previously. We will also use these large datasets to develop a simple method to identify which Australian women are most likely to carry a fault in BRCA1 or BRCA2, based on their personal and family cancer histories. This study will assist genetic counsellors inform Australian women who consider mutation testing for BRCA1 and BRCA2 about their cancer risks, and help make breast cancer genetics more cost effective.Read moreRead less
Analysis Of HIV Virologic Response-rebound Data: Prognostic Indicators Of Post-HAART Viral Control
Funder
National Health and Medical Research Council
Funding Amount
$144,000.00
Summary
The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to ....The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to initiate treatment sufficiently early in order to avoid irreversible damage balanced by the problems of potential viral resistance or toxicity if started too soon. Determination of factors which will assist practitioners to optimise the timing of treatment initiation remains a high priority. Our aim in this project is to develop and study the use of novel statistical mixed-effects models designed to analyse factors associated with visit-time viral load data following commencement of therapy, taking account of the entire follow-up profiles of responses over time. The project involves both theoretical and empirical analyses of the estimation and inferential properties of the mixed-model method in conjunction with comprehensive analyses of prognostic factors associated with post-treatment virologic control in patients from the Western Australian HIV Cohort Study. These include demographic, virologic, immunologic, adherence and host genetic factors. The statistical methods developed will have wide applicability and add significantly to the suite of procedures available for the analysis of longitudinal response data.Read moreRead less
Statistical Methods To Assist The Control Of Communicable Diseases, And Their Application
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A range of programs, such as vaccination schedules and intervention in outbreaks, is in place to reduce our burden of illness from infectious diseases. This project aims to develop new methods, based on models and associated statistical analyses, to help ensure that our control programs are based on the best available evidence. There are five specific themes: 1. Developed methods for predicting major outbreaks of diseases and appy them to Australian data on measles, pertussis and Ross River viru ....A range of programs, such as vaccination schedules and intervention in outbreaks, is in place to reduce our burden of illness from infectious diseases. This project aims to develop new methods, based on models and associated statistical analyses, to help ensure that our control programs are based on the best available evidence. There are five specific themes: 1. Developed methods for predicting major outbreaks of diseases and appy them to Australian data on measles, pertussis and Ross River virus. The new methods will enable timely intervention to reduce the population risk from these diseases, and to guide the proposed elimination of measles from Australia. 2. The current concept of vaccine efficacy, which is central to the epidemiological assessment of vaccines, performs poorly when the vaccine provides only partial protection, when immunity wanes over time and when infected vaccinees have a lower infectivity. A concept of vaccine efficacy will be developed that overcomes these weaknesses. This concept will find widespread use in epidemiology. 3. Data available from 80 outbreak investigations of transmissible diseases will be analysed to assess the relative effectiveness of various intervention steps. 4. A comprehensive model, and associated computer software, will be developed as a tool for assessing the relative merits of different vaccination schedules. It will be applied to address Australian policy issues for vaccination against pertussis, chickenpox and rubella. 5. The method of backprojection for estimating trends in HIV infection and predicting AIDS incidence will be enhanced to incorporate newly available data in which HIV and AIDS diagnoses are linked. This will enable a precise assessment of infection incidence among heterosexuals and other exposure categories with relatively few cases, to ensure that HIV does not spread more widely.Read moreRead less