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.
TRACEBACK - Identification Of Women Carrying Germline BRCA1/2 Mutations Through A Retrospective Analysis Of Patients Diagnosed With High Grade Serous Ovarian Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$83,284.00
Summary
Inheriting a mutated-BRCA is associated with significant risk of developing cancer. It is a crucial diagnosis to make with proven procedures that can reduce the risk of cancer developing. Ovarian cancer (HGSOC) is the tumour most strongly associated with BRCA (15-20%) and provides a diagnostic opportunity, but despite Australian guidelines <50% receive testing. Our aim is to provide BRCA1/2 screening opportunities to patients and families and improve the rate of BRCA testing Australia wide.
Population Based Genetic Testing For High-risk Breast And Ovarian Cancer Predisposition Genes
Funder
National Health and Medical Research Council
Funding Amount
$1,112,985.00
Summary
Inherited mutations in BRCA1 and BRCA2 confer a very high risk of breast and ovarian cancer. Importantly, once carriers are identified, effective strategies are available that can dramatically reduce the risk of cancer. We will perform genetic testing of a healthy western population to identify breast/ovarian cancer genes before the women develop cancer. Population-based screening could significantly reduce the incidence of these diseases.
The Mutagenic Influence Of 5-methylcytosine And Its Relevance For Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$844,462.00
Summary
Over time our cells accumulate damage to their DNA, which introduces mistakes in the genetic code. These mistakes can alter genes that regulate cell growth and survival and, in this way, they begin the process of turning a normal cell into a cancer. This research is investigating the cellular repair mechanisms that safeguard against DNA damage. Manipulating these repair mechanisms may offer a new way to treat cancer, by selectively inducing DNA damage within cancer cells.
Genetics And Genomics Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$714,745.00
Summary
Our knowledge of the number and nature of the genes involved in breast and ovarian cancer is limited. To rapidly define the critical breast and ovarian cancer-causing genes my laboratory uses an integrative genomics approach whereby information from several genome-wide platforms are combined. A key initiative that will underpin much of our work is Lifepool, which is a unique cohort of 100,000 Victorian women attending BreastScreen that will support a range of research into breast cancer.
Young Onset Colorectal Cancer: Genetics Pathology And Environment
Funder
National Health and Medical Research Council
Funding Amount
$439,180.00
Summary
There has been a steady increase since 2002, in the age-standardised incidence of CRC in males under 45 years in Australia, contrasting with the stabilisation in incidence of CRC in males of age 45 years and over. Persons under 50 years are not routinely screened unless they have a significant family history of CRC. Young-onset rectal cancer is associated with late presentations and with a higher mortality. This proposal will address the possible risk factors for young-onset CRC.
Germline Epimutations Of Tumour Suppressor Genes In Familial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$502,500.00
Summary
In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called ....In the case of bowel cancer, studies of the pattern of disease in our community indicate that up to 20% of all bowel cancers has a inherited component . We now know the genetic abnormality in up to 4% of these cases. We have recently discovered a previously unrecognised cause of cancer. Individuals who are affected by this disease may have cancer in the bowel, as well as the breast and womb. In this condition the gene alphabet is correct but the genes are chemically modified. This change called methylation means that certain genes are spelt incorrectly or not at all. To date we have found two individuals who have this problem. Our work has shown that these individuals have inherited a genetic change and potentially could pass this change on to their offspring. This grant application seeks to formally pursue this findng. We will study a group of people in whom the genetic cause for their cancer remains unknown. Blood samples from these individuals will be examined for methylation of their DNA. A successful project will lead to a full description of this new type of hereditary cancer, and thus serve as the basis for identifying and effectively managing people and families at risk of this disease. It is likely that identification of individuals who are 'at risk' of cancer will allow us to implement preventative screening strategies. We will also be able to provide reassurance to those family members who have not inherited the methylation abnormality.Read moreRead less
New High-risk Variants For Colorectal Cancer: The Post-GWAS Era
Funder
National Health and Medical Research Council
Funding Amount
$710,105.00
Summary
Our aim is to discover new genes that greatly increase bowel cancer risk. If we can identify these carriers we may be able to prevent them getting cancer. By studying DNA related to bowel cancer, using a novel family design, we will identify families most likely to carry the new genes. We will focus genetic testing, using new techniques, to look for mutations in these prioritised families. Identified mutations will be tested in a 3,500 bowel cancer cases to see how important they are.
A/Prof Thomas' Senior Research Fellowship will provide support for the continued development of a broad-based, national and international research program focused on the biology and clinical aspects of connective tissue tumours. A/Prof Thomas' career goals are to continue work in basic, translational and clinical research into these tumours which include osteosarcoma, liposarcoma, giant cell tumour of bone and the inherited risk of development of these neoplasms.