KConFab - The Kathleen Cuningham Foundation Consortium For Research Into Familial Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$2,176,975.00
Summary
Breast cancer is the most common malignant disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australasian-wide study is to complete collection of clinical, epidemiological and genetic data on 1,600 of these severely-affected families. The national resource is, and will continue to be, of great value for researchers who want to identify and characterize the genetic and life style factors that a ....Breast cancer is the most common malignant disease of women. In families with an inherited form of breast cancer, nearly half the women in every generation can develop the disease. The aim of this Australasian-wide study is to complete collection of clinical, epidemiological and genetic data on 1,600 of these severely-affected families. The national resource is, and will continue to be, of great value for researchers who want to identify and characterize the genetic and life style factors that affect onset and progression of the disease.Read moreRead less
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
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
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
Breast Cancer is a very common disease in women and although huge progress has been made in the last two decades, much remains to be done to improve our understanding of different types of breast cancer and its management. This program brings together the expertise of three senior researchers: 2scientists and 1 medical scientist. Dr Trench has an interest in identifying genes involved in cancers arising in patients who have a strong family history. She will use molecular methods and cohorts of p ....Breast Cancer is a very common disease in women and although huge progress has been made in the last two decades, much remains to be done to improve our understanding of different types of breast cancer and its management. This program brings together the expertise of three senior researchers: 2scientists and 1 medical scientist. Dr Trench has an interest in identifying genes involved in cancers arising in patients who have a strong family history. She will use molecular methods and cohorts of patients enrolled with Kathleen Cunningham Foundation for Research into Familial Breast and Ovarian Cancer to identify the genes responsible, assess their distribution in the population and determine whether these genes also play a role in non-familial cancers. Dr Khanna's work examines the complex array of enzymes that are responsible for maintaining the integrity of the DNA, and investigates how failure of these mechanisms leads to damage of the genetic material which ultimately results in cancer. It is known that genes involved in familial predisposition code for proteins that work as DNA repair enzymes. It is also known that different types of breast cancer exist, each with differing behaviour and response to treatment and that they are associated with specific genetic changes, including those associated with a familial predisposition. Prof Lakhani's interest lies in using microscopy and the latest molecular tools to refine the classification of these different types of breast tumour so that they can be managed appropriately by his surgical and oncological colleagues. A better understanding of the genetic changes and underlying biology of different types of breast cancer will lead to individualised and specific therapy for patients. This program brings together a unique combination, nationally and internationally, that investigates cancers at the level of genes and cells and translates the information to the clinic for the benefit of patient management.Read moreRead less
Intraductal Carcinoma Of The Prostate: Indicator Of Aggressive Disease.
Funder
National Health and Medical Research Council
Funding Amount
$884,377.00
Summary
This proposal addresses the need to improve personalised treatment decisions for men with high risk familial prostate cancer as they have a very aggressive disease progression with a very poor clinical outcome. We will perform biological and pre-clinical studies to improve the clinical diagnosis, prognosis and treatment options for men with germline mutations in BRCA2 or BRCA1 genes who develop prostate cancer.
STICs And STONes: A Randomised, Phase II, Double-Blind, Placebo-Controlled Trial Of Aspirin In Chemoprevention Of Ovarian Cancer In Women With BRCA1 And BRCA2 Mutations
Funder
National Health and Medical Research Council
Funding Amount
$653,892.00
Summary
Women with a BRCA1 or BRCA2 gene abnormality are at increased risk of ovary and fallopian tube (O&FT) cancers and often have their O&FTs removed to prevent cancer. Microscopic cancers are often seen at the time of surgery. Some studies suggest that aspirin might reduce O&FT cancer risk. This study will assign women to daily aspirin or placebo for 6-24 months before their preventive O&FT surgery. It will provide a better understanding of how O&FT cancers start and the influence aspirin may have.
Collaborative Ovarian, Prostate And Breast Gene-environment Study (COGS)
Funder
National Health and Medical Research Council
Funding Amount
$447,383.00
Summary
The EU-COGS application has arisen from genome wide scans that identify common genetic variants associated with breast, ovarian and prostate cancer risk. Our studies contributed 50% of DNA samples to the prostate cancer genome wide scan. COGS will now measure these variants in a large number of cases and controls from an international consortium of studies to test whether genetic risks are modified by other genes or lifestyle factors. This will better define genetic risks and identify men at inc ....The EU-COGS application has arisen from genome wide scans that identify common genetic variants associated with breast, ovarian and prostate cancer risk. Our studies contributed 50% of DNA samples to the prostate cancer genome wide scan. COGS will now measure these variants in a large number of cases and controls from an international consortium of studies to test whether genetic risks are modified by other genes or lifestyle factors. This will better define genetic risks and identify men at increased risk who should be the focus of appropriate screening and prevention strategies. Australian participation in the prostate cancer genome wide scan helped to identify a number of genetic variants associated with prostate cancer risk. The aim of EU-COGS, which needs large numbers of samples with epidemiological, tumour pathology and clinical information, is to determine whether these genetic variants act singly or together and the extent to which lifestyle and environmental factors can modify the genetic risk. Our contribution of >10% of the total DNA samples to COGS will enable us to understand how such genetic risks can be modified in the Australian environmental context.Read moreRead less