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
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
Risk Factors, Screening, Prophylaxis And Outcomes In Individuals From Breast Cancer Families: KConFab Follow-Up Study
Funder
National Health and Medical Research Council
Funding Amount
$510,675.00
Summary
Having a strong family history of 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 gene abnormalities via Family Cancer Centres around Australia. However, once a gene abnormality is found, little is known about the best ways to prevent cancer or detec ....Having a strong family history of 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 gene abnormalities via Family Cancer Centres around Australia. However, once a gene abnormality is found, little is known about the best ways to prevent cancer or detect it early. The Kathleen Cuningham Consortium for Research into Familial Aspects of Breast Cancer (kConFab) has been recruiting families with exceptionally strong histories of breast cancer since 1997. kConFab is funded to collect epidemiological information and biological specimens on such individuals only at the time of their initial recruitment. In 2000 the NHMRC recognised the importance of undertaking clinical follow-up of this precious cohort of individuals, and provided funding through a 3 year project grant to commence the first round of 3 yearly follow-up on this cohort (NHMRC Project Grant #145684). The first 2 years of this follow-up has been completed successfully and the current is application is for a renewal of funding (to commence in 2004) to enable us to undertake further follow-up of the now much larger cohort. In the short term we will examine the screening and preventive surgery behaviours of high risk women within this study to determine whether they are optimal. The ultimate aim of this long term follow-up of individuals in kConFab is to determine what factors impact on the development of cancer in well individuals with a genetic predisposition to breast cancer.Read moreRead less
Studies On Mechanisms Of Vesicular Trafficking And Catalysis For The Menkes (MNK) Copper-transporting P-type ATPase
Funder
National Health and Medical Research Council
Funding Amount
$363,757.00
Summary
Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal cop ....Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal copper deficiency disorder in humans, and the diverse and detrimental symptoms of this disease related to organs and tissues described above is a stark indicator of the essentiality of copper. We have carried out extensive research on Menkes disease and in particular the Menkes protein which in normal individuals plays a major role in maintaining the copper balance in cells, i.e. enough Cu to satisfy nutritional needs of cells but not too much which causes toxicity. The normal Menkes protein catalyses the transport of Cu across membranes of cells to the areas where it is needed by copper-dependent enzymes which themselves catalyse important chemical reactions. The normal Menkes protein functions as a molecular pump. We have discovered that this protein can OsenseO Cu concentrations in the cell and when these reach potentially toxic levels it can move (traffick) via small vesicles to the plasma membrane which surrounds cells. There it pumps the excess Cu out of the cell and returns to its original location. Our studies are directed to understanding the molecular mechanisms which permit this remarkable protein to achieve a copper balance in living cells. The findings will be of major significance in understanding and treating acquired and inherited diseases involving copper deficiency or copper toxicity.Read moreRead less
Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
Genetic Bases For Charcot-Marie-Tooth And Hereditary Sensory Type 1 Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$618,055.00
Summary
This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradua ....This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradually increasing disability eventually requiring splints and other walking aids. We propose to use the newly developed resources of the human genome project to locate the defective gene. In previous studies we have used these methods to locate the defective genes of 2 other hereditary diseases of nerve. In this study we propose to investigate a newly recognised form of CMT called intermediate CMT. Intermediate CMT has characteristics intermediate between the better known forms of CMT affecting the nerve itself (the axon) or the nerve insulation (the surrounding myelin sheath). The disorder may therefore affect both components of nerve. The affected gene may mediate communication between the nerve and its sheath. This research should give valuable insight into the mechanisms responsible for the maintenance of normal nerve. Finding the gene may therefore have relevance to many other diseases of nerve. This research is a systematic search and should lead to the abnormal gene causing the disease. Once the gene involved is known then an effective test will be developed. When we can test for the disease, we probably will find that the disorder is much more common than previously recognised. Knowledge of the function of this gene will lead to an understanding of how the disease develops and will eventually lead to effective treatments.Read moreRead less
Regulation Of Liver Iron Loading In Hereditary Haemochromatosis
Funder
National Health and Medical Research Council
Funding Amount
$663,188.00
Summary
Hereditary haemochromatosis is a common iron overload disorder. It affects 1 in 200 Australians causing liver iron overload, fibrosis, cirrhosis and cancer. The severity of liver iron overload in haemochromatosis is variable. In this study we will determine whether factors that are known to regulate iron metabolism such as iron levels, oxidative stress and inflammation modify liver iron transport systems and the degree of liver iron loading in animal models of haemochromatosis.
A Randomised Trial Of A Decision Aid For Women At Increased Risk For Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$115,110.00
Summary
Epithelial ovarian cancer is the leading cause of death from gynaecological malignancy in Australia. The majority of women with ovarian cancer are diagnosed with advanced disease, and the chance of cure is low. The strongest risk factor for ovarian cancer identified to date is a family history of ovarian cancer, and up to 5% of all ovarian cancers are thought to be due to dominantly inherited mutations in a small number of ovarian-cancer-related genes. National guidelines on surveillance and pro ....Epithelial ovarian cancer is the leading cause of death from gynaecological malignancy in Australia. The majority of women with ovarian cancer are diagnosed with advanced disease, and the chance of cure is low. The strongest risk factor for ovarian cancer identified to date is a family history of ovarian cancer, and up to 5% of all ovarian cancers are thought to be due to dominantly inherited mutations in a small number of ovarian-cancer-related genes. National guidelines on surveillance and prophylactic strategies have recently been ratified. These are largely based on expert opinion. Because of the uncertain efficacy of ovarian cancer screening and the high mortality associated with ovarian cancer, prophylactic oophorectomy is considered an option for women at high risk. Decisions about optimal care are difficult for both women and their doctors. Efforts to improve services for women who are trying to make informed decisions about screening and prophylactic strategies under conditions of uncertainty must be informed by sound knowledge of the efficacy of educational interventions. Decision aids have been developed as adjuncts to practitioners' counselling to prepare patients for decision-making. The proposed randomised controlled trial will compare the efficacy of a general educational pamphlet and that of a tailored decision aid. A total of 120 women at risk for ovarian cancer who are attending one of five familial cancer clinics will be included in the trial to determine the efficacy of different educational interventions in preparing women for decision-making about screening and prophylactic options.Read moreRead less