Thyroid cancer is the commonest endocrine malignancy, and typically affects younger adults. Despite low mortality rates, local recurrence is not uncommon and re-operative surgery can cause significant morbidity. We are studying genetic variants in thyroid transcription factors associated with thyroid cancer predisposition. Our work will determine the mechanism of this association, and provide new strategies for early diagnosis and prevention of thyroid cancer.
Improving Cancer Outcomes In Under-studied Cancers By Understanding Their Risk Factors And Patterns Of Cancer Care.
Funder
National Health and Medical Research Council
Funding Amount
$421,747.00
Summary
Cancer is the second leading cause of disease burden in Australia. Much can be done to reduce this burden through effective cancer prevention and ensuring all patients receive optimal evidence-based care. This research focuses on thyroid, kidney and ovarian cancer and aims to increase knowledge of these cancers’ causes and to investigate variation in patient care and its impact on outcomes. Ultimately the objective of the work is to decrease Australia’s cancer burden.
Understanding The Role Of RAS Mutations In Thyroid Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$463,854.00
Summary
My fellowship will examine the association of RAS mutations in thyroid cancer. RAS proteins are the most mutated in cancer and I will investigate how they work in thyroid cancer. RAS mutated thyroid cancer is more likely to cause death. This grant will be based in the pioneering lab of Prof Fagin at Memorial Sloan Kettering Cancer Center and the Garvan Institute of Medical Research. It is hoped by understanding these mutations, new treatments for thyroid cancer can be developed.
Thyroid hormones are regulators of development and metabolism. The lack of concordance of thyroid function and disease in identical twins suggests that environmental effects have a significant role. Quantifying epigenetic modifications, such as DNA methylation, has the potential to identify causal effects from the environment. This research will provide a comprehensive database of DNA methylome alterations that will contribute important insights into thyroid function in health and disease.
Understanding Causes Of The Rising Incidence Of Thyroid Cancer – What Can Mutations In The BRAF Oncogene Tell Us About Causes And Diagnostic Pathways For Thyroid Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$610,222.00
Summary
The occurrence of thyroid cancer has increased rapidly over the last 25 years but the cause is unknown. The increase may reflect ‘over-diagnosis’ of less harmful cancers or greater exposure to causes of this cancer. Evidence suggests that a gene mutation (BRAF) in thyroid cancers is important in understanding the drivers of the increase. This study will examine the increase in thyroid cancer by investigating causes and diagnostic pathways considering the presence or absence of BRAF mutations.
The Identification Of Novel Genes Involved In The Initiation And Development Of Thyroid Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid c ....Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid cancer. However mutations, mistakes in the genetic code, of these genes account for only a small percentage of thyroid tumours and none of these genes have been shown to be useful as clear prognostic markers for tumour progression or aggressiveness. The merging of the 2 fields of cytogenetics (the study of chromosomes) and molecular genetics (the study of genes at the DNA and RNA level) has strengthened our ability to understand the process of tumour development. We are proposing use of a technique called Comparative Genomic Hybridisation to aid in the identification of new genes associated with tumour development in both benign and malignant thyroid disease. This technique has already been used to aid in the location of genes with a role in ovarian and brain cancer and in some familial syndromes characterised by breast and gastrointestinal malignancies. This method involves the detection of regions of chromosomal amplifications or deletions in tumour DNA that is fluorescently labelled (green), mixed with normal human DNA also fluorescently labelled (red). If the tumour contains regions of amplification (likely housing an oncogene), analyses show increased green fluorescence and if deletions are present (likely housing a tumour suppressor gene), analyses show increased red fluorescence. Chromosomal regions identified by this method will be further analysed to identify the precise genes they contain and establish a role for these genes in the development of thyroid tumours.Read moreRead less
Nuclear Receptors And Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$681,979.00
Summary
This project will explore the potential for a nuclear receptor known as the thyroid receptor to suppress growth of breast cancer using cell culture models and mouse models. We hope to show that activating the thyroid receptors leads to a reduction in breast cancer growth providing evidence that the thyroid receptor pathway could be targeted for therapy.
Identification Of Genetic Variants Regulating Thyroid Function In Health And Disease By Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$316,433.00
Summary
Small differences in thyroid function are associated with important clinical outcomes including longevity and cardiovascular disease. We recently completed a Genome Wide Association Study and identified a novel locus associated with blood levels of Thyroid Stimulating Hormone. In this project we will extend that research to study rare genetic variants and examine their association with thyroid function in health and disease.