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
Mapping And Identification Of Novel Breast Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$354,419.00
Summary
Breast cancer is one of Australia?s major cancer problems, but we still do not fully understand why certain people are at higher risk of the disease than others. In recent years two genes have been shown to be abnormal in a small number of people with strong family history of breast cancer and-or ovarian cancer. This study will search for the identity of other genes of this kind. It will take advantage of a large network of researchers which has been working to recruit women with a strong family ....Breast cancer is one of Australia?s major cancer problems, but we still do not fully understand why certain people are at higher risk of the disease than others. In recent years two genes have been shown to be abnormal in a small number of people with strong family history of breast cancer and-or ovarian cancer. This study will search for the identity of other genes of this kind. It will take advantage of a large network of researchers which has been working to recruit women with a strong family history of breast cancer from around Australia over the last two years. In this short time such large numbers of women have come forward that a study of this kind will be among the largest in the world. The results of this research, in terms of location of possible new genes causing high risk of breast cancer, will be shared with other researchers in Europe and the US who are working toward the same goals. This will ensure that progress is as rapid as possible. Based on experience with the two previously discovered breast cancer genes, this research will also shed light on the types of changes that drive the malignancy of breast cancer cells. It will have implications for improved prevention, diagnosis and treatment of breast cancer.Read moreRead less
Investigating Tumour Initiation And Growth In A Panel Of Mice Defective In Epigenetic Reprogramming.
Funder
National Health and Medical Research Council
Funding Amount
$421,600.00
Summary
Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatme ....Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatments in humans.Read moreRead less
Microarray-targeted Candidate Gene Approach To Finding Ovarian Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$612,933.00
Summary
We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them t ....We propose that subtle, heritable changes in the expression or function of genes that are switched off, or on, early in the development of ovarian tumours, may predispose the individual to ovarian cancer. We will are carry out a large study of the most common subtype of ovarian adenocarcinoma, serous invasive tumors, in order to identify genes that affect a woman's risk of ovarian cancer. Identification of women at elevated risk for ovarian cancer on the basis of their genotype will allow them to be targeted for screening, and for intervention studies, as well as providing fundamental insight into the etiology of ovarian cancer.Read moreRead less
A Piggy-back Screen For Genes Involved In Cancer Epigenetics
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
Cancer can be caused not only by mutations in genes, but also by changes to our epigenome, which controls whether genes are on or off. There is much still to learn about the epigenome. We have developed a method to identify epigenome regulators. The epigenome is disrupted in cancer, but it is not know whether this starts tumour growth. I will use mutant mice to study this and analyse human cancers for mutations in epigenome regulators. This may lead to preventative screening and new treatments.