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
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
KConFaB - A CONSORTIUM FOR RESEARCH ON FAMILIAL BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$1,624,711.00
Summary
Breast cancer is the most common 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 Australia-wide study is to collect clinical, epidemiological and genetic data on approximately 700 of these severely-affected families. This national resource will be of great value for researchers who want to identify and characterize the genetic and life-style factors that affect the onset and progression of t ....Breast cancer is the most common 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 Australia-wide study is to collect clinical, epidemiological and genetic data on approximately 700 of these severely-affected families. This national resource will be of great value for researchers who want to identify and characterize the genetic and life-style factors that affect the onset and progression of the disease. The data emerging from the study will lead to more accurate genetic counselling, better surveillance and, ultimately, better methods to prevent and treat the disease in families who inherit a predisposition to the disease.Read moreRead less
The human hepatitis B virus (HBV) is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Acute HBV infection can produce extreme variation in disease, ranging from asymptomatic infection, to acute transient hepatitis with jaundice, or fulminant hepatitis leading to liver failure (Hollinger, 1996). The identification of viral genes that affect the severity of disease is a major current goal in medical virology. For example, there is considerable ....The human hepatitis B virus (HBV) is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Acute HBV infection can produce extreme variation in disease, ranging from asymptomatic infection, to acute transient hepatitis with jaundice, or fulminant hepatitis leading to liver failure (Hollinger, 1996). The identification of viral genes that affect the severity of disease is a major current goal in medical virology. For example, there is considerable interest in identifying the genes of the influenza genome responsible for high mortality outbreaks; with the human immunodeficiency virus, the virus that causes AIDS, variants deleted in the nef gene region cause a less rapidly progressing infection and have attracted attention as a possible prototype for an attenuated vaccine. We propose to investigate how the different genes of hepadnaviruses affect the course of infection and type of disease produced. Studies will be performed in ducks infected with the duck hepatitis B virus (DHBV) as these animals provide the only model system available in Australia. We will study both experimentally and naturally derived DHBV variants to explore the effects of genetic changes on the outcome of infection. This will enhance our understanding of this virus family and will provide models for comparison with HBV infection. This knowledge may then contribute to our ability to manage and control HBV disease in humans.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
Genetic Pathology Of Roquin In Human Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$495,466.00
Summary
Lupus is a life-threatening disease in which immune responses normally targeted at germs are directed at tissue in the body. We have discovered a mouse model of lupus and elucidated an important pathway that determines whether immunity is directed at the body or at germs. Building on recent progress in understanding the genetic variation between individuals, we will use the information obtained from the mouse model to investigate the genes that regulate this pathway in people with lupus.
Clinical Outcomes In Individuals With An Inherited Predisposition To Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,015.00
Summary
Genes have recently been identified which, when abnormal, result in an inherited tendency towards developing breast cancer (BC). It is now possible to undergo testing for abnormalities in these genes. However, there is little known about the best ways to prevent cancer or detect it early in individuals with such a gene abnormality. In addition, it is possible that BCs occuring in women with a gene abnormality might behave differently (have a different prognosis and thus require different treatme ....Genes have recently been identified which, when abnormal, result in an inherited tendency towards developing breast cancer (BC). It is now possible to undergo testing for abnormalities in these genes. However, there is little known about the best ways to prevent cancer or detect it early in individuals with such a gene abnormality. In addition, it is possible that BCs occuring in women with a gene abnormality might behave differently (have a different prognosis and thus require different treatment) from other BCs. Answers to these important questions are essential for women to be able to make informed decisions about how best to reduce their risk of developing, or dying from, BC. This study will examine the clinical outcomes of individuals (both those who have not yet developed cancer and those who have) with an inherited tendency to BC. The study has 2 components; each builds on one of 2 existing Australian studies of hereditary BC 1) Is the likely clinical outcome (prognosis) different for BC patients with a gene abnormality compared to those without? The cancer and treatment details of BC patients in Melbourne and Sydney who are already enrolled in the Australian Breast Cancer Family Study will be examined to determine whether those with a gene abnormality have a better or worse outcome than those without. 2) What factors impact on the clinical outcome (development of cancer) in well individuals with an inherited tendency to BC? An Australia-wide study of inherited BC (kConFab) has recruited families with a strong family history of BC. The family history, lifestyle, exposure to female hormones, cancer screening and preventive surgery details of all individuals in the study will be collected 3 years following study entry. Ultimately this information should help determine how best to prevent cancer in such individuals.Read moreRead less