The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
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
I am a clinician-scientist engaged in basic, translational and clinical breast cancer research, with the long-term goal to identify and exploit novel cancer targets to improve patient outcomes. My research, which covers both sporadic and hereditary forms of breast cancer, is focussed on elucidating the breast epithelial cell hierarchy, in order to identify key regulators responsible for breast epithelial cell proliferation, differentiation and cancer.
I am a cellular biologist studying lineage commitment and differentiation in the mammary gland. Key interests include defining transcriptional regulators that are important for mammary gland development and oncogenesis, and the characterisation of stem cells and other epithelial cell types in breast tissue.
Prof Lindeman's laboratory, co-headed with Dr Visvader, has played an influential role in the identification of mammary stem and progenitor cells, elucidation of the mammary epithelial cell hierarchy and gaining insights into how female hormones regulate mammary gland development and cancer. In parallel, I have established translational research platforms such as patient-derived tumour xenograft (PDX) models, which offer powerful preclinical models to test new drugs.
Genetic Variants, Phenotypic Spectrum And Breast Cancer Risk Associated With Germline Mutations In PALB2: Identifying Female PALB2 Mutation Carriers At The Time Of Diagnosis
Funder
National Health and Medical Research Council
Funding Amount
$45,093.00
Summary
Population studies of female breast cancer (BC) show only a small proportion of familial aspects of BC can be explained by current knowledge of its causes. Women carrying PALB2 mutations who also have a strong family history of BC are of increased risk of BC. Our work will further define the risks and devise criteria to identify women most likely to carry PALB2 mutations. This will help prioritize testing, classify PALB2 variants and provide appropriate clinical management to carriers.
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
Integration Of Genetic Testing For Risk Associated Genomic Variants And Rare Predisposition Genes Into The Management Of High Risk Hereditary Breast Cancer Families
Funder
National Health and Medical Research Council
Funding Amount
$645,457.00
Summary
Breast Cancer is a common disease with up to 20% of cases associated with a family history. This project aims to assess the contribution of recently identified risk associated genomic variants and rare predisposition genes to the heritability of familial breast cancer. The project will also assess the experience of clinicians and patients as we aim to use this information to help improve the process of risk assessment and genetic counselling in the specialist Familial Cancer Centres.