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
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
KConFab Follow-Up Project: A Prospective Study Of Non-Genetic Risk Modifiers In Women At High Risk For Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$726,351.00
Summary
Having a strong family history for breast cancer is one of the most important risk factors for the disease. Two major genes, BRCA1 and BRCA2, have been identified which, when abnormal, result in an inherited tendency towards developing breast cancer. Women with a strong family history of breast cancer can undergo testing for these genes via Family Cancer Centres around Australia. However in only about 20% of families with a strong family history will a gene abnormality be discovered. Women from ....Having a strong family history for breast cancer is one of the most important risk factors for the disease. Two major genes, BRCA1 and BRCA2, have been identified which, when abnormal, result in an inherited tendency towards developing breast cancer. Women with a strong family history of breast cancer can undergo testing for these genes via Family Cancer Centres around Australia. However in only about 20% of families with a strong family history will a gene abnormality be discovered. Women from families in which no abnormality has been discovered remian at high risk because they may have an abnormality in an as yet undiscovered gene which can't yet be tested for. Little is currently known bout the best ways to prevent cancer in women who are at high risk. The Kathleen Cuningham Consortium for Research Into Familial Aspects of Breast Cancer (kConFab) has been recruiting families with exceptionally strong hostories of breast cancer since 1997. kConFab is funded to collect risk factor information on such individuals only at the time of their initial recruitment. In 2000 and again in 2003, the NHMRC recognised the importance of undertaking clinical follow-up of this precious cohort of individuals and provided funding through consecutive project grants to do so. The current application is to enable us to continue that follow-up for a further 5 years. As well as continuing the follow-up, we will use the data already collected to examine the effect of prophylactic surgery, breastfeeding and use of the oral contraceptive pill as well as cigarette smoking and alcohol use on breast cancer risk in high-risk women. The results of this study will provide high-risk women with better information about what modifications they might make to their lifestyles to reduce their cancer risk.Read moreRead less
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
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.