A Vulvar Cancer Cluster In Young Indigenous Women In Arnhem Land: Investigation Of Community Knowledge, Genetic Susceptibility And Supportive Care Response
Funder
National Health and Medical Research Council
Funding Amount
$711,841.00
Summary
Cancer of the vulva is 50 times more common in young Aboriginal women in Arnhem Land than in other women. Human Papillomavirus (HPV), which also causes cervical cancer, is the usual cause of this cancer; initial investigations have found that HPV is present in these cancers but is not the reason for the excessive incidence. This study will investigate local knowledge about this disease, and whether inherited susceptibility or an environmental cancer-causing substance are the cause of the excess.
Massively Parallel Sequencing And PCR Optimised For DNA-based Diagnostics And Discovery
Funder
National Health and Medical Research Council
Funding Amount
$201,664.00
Summary
The next generation of medical diagnostics and discovery in disease research will involve the marriage of PCR, a tool used to amplify large amounts of DNA from small starting quantities, and �next generation� sequencing, a way to sequence lots and lots of DNA on a single instrument run. This study aims to describe methods which allow scientists to screen hundreds of disease genes in hundreds of people simultaneously with high accuracy and high efficiency.
Genome-wide Study Of Loss Of Heterozygosity Using High Density SNP Arrays To Identify Breast Cancer Predisposition Genes
Funder
National Health and Medical Research Council
Funding Amount
$542,599.00
Summary
The genes responsible for the majority of breast cancer families remain unknown. The genes BRCA1 and BRCA2 can prevent the development of cancer and represent a class of gene known collectively as 'tumor suppressors'. One of the hallmarks of these genes is that they show loss of the normal copy of the gene in tumors that arise in individual carrying one inherited, mutated copy. The broad aim of this proposal is to exploit this phenomenon to identify novel tumor suppressor genes that predispose t ....The genes responsible for the majority of breast cancer families remain unknown. The genes BRCA1 and BRCA2 can prevent the development of cancer and represent a class of gene known collectively as 'tumor suppressors'. One of the hallmarks of these genes is that they show loss of the normal copy of the gene in tumors that arise in individual carrying one inherited, mutated copy. The broad aim of this proposal is to exploit this phenomenon to identify novel tumor suppressor genes that predispose to familial breast cancer. This will be done by analyzing tumors from families that do not have either BRCA1 or BRCA2 mutations. Candidate tumor suppressor genes will be identified when tumors from different individuals in the same family all appear to have lost one copy of a gene, and retained the same copy, in a particular chromosomal region. We study tumours from non-BRCA1-2 breast cancer families using genetic techniques that are able to rapidly and accurately identify which parts of the chromosomes have been lost. Families will be identified in which all the tumors have lost exactly the same part of the chromosome. Next, we will exploit the fact that the entire sequence of the human genome is completed to find out which genes are located within the candidate region. We will then apply other technologies to identify which of these 'candidate genes' is actually responsible for the cancer in that family. Following this, we will investigate other families with a history of breast cancer to see how many can be accounted for by mutations in this gene. It is possible that we may identify more than on breast cancer gene using this powerful approach. Identification of new breast cancer predisposition genes would have major clinical relevance to the families directly affected, and much wider relevance if the same gene (or pathway) is later found to be involved in the causes of other familial or sporadic breast cancers.Read moreRead less
Identification Of New Mutations That Contribute To Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$323,825.00
Summary
Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the genetic defects that contribute to disease initiation and progression. Although a number of breast cancer susceptibility genes have been identified, the contribution each of these genes makes to breast cancer susceptibility is currently unclear. This is partly due to limitations in current diagno ....Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the genetic defects that contribute to disease initiation and progression. Although a number of breast cancer susceptibility genes have been identified, the contribution each of these genes makes to breast cancer susceptibility is currently unclear. This is partly due to limitations in current diagnostic processes and an incomplete understanding of all of the genetic elements for which disruption can lead to loss of gene function. This proposal aims to identify regulatory pathways that are critical for the expression of an important breast cancer gene called BRCA1. Furthermore, it aims to determine the status of these pathways in breast cancer patients, thus expanding our knowledge of the actual contribution that disruption of this gene makes to this disease. It also aims to determine the potential for trans-acting factors to regulate the expression of BRCA1 and thus activity of the BRCA1 pathway. The predicted outcome of this research is an improved ability to perform presymptomatic diagnostic testing for breast cancer and the ultimately the development of more effective drugs to treat certain breast tumours.Read moreRead less
The Role Of Differentially Methylated Genes In The Initiation And Progression Of Colorectal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$361,527.00
Summary
Most colorectal cancers develop from polyps in the lining of the bowel. The bulk of cancers develop from adenomatous polyps, but we have found that a second type of polyp called a hyperplatic polyp can also be associated with the development of cancer. During our studies of these polyps we found that a particular gene was inactivated in all of these polyps. We have called this gene HPP1. HPP1 was also found to be inactivated in adenomatous polyps and about 50% of colorectal cancers, indicating t ....Most colorectal cancers develop from polyps in the lining of the bowel. The bulk of cancers develop from adenomatous polyps, but we have found that a second type of polyp called a hyperplatic polyp can also be associated with the development of cancer. During our studies of these polyps we found that a particular gene was inactivated in all of these polyps. We have called this gene HPP1. HPP1 was also found to be inactivated in adenomatous polyps and about 50% of colorectal cancers, indicating that it may be an important player in the early stages of colorectal cancer and hence may allow opportunity for prevetive intervention. This grant proposal will investigate the function of HPP1 in the genesis of colorectal polyps and cancers.Read moreRead less
Understanding The Development Of Pancreatic Islet Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$579,163.00
Summary
We will use mouse models of pancreatic cancer that we have established previously to investigate the molecular basis of the development and progression of tumours in the insulin-producing cells of the pancreas. We propose to manipulate a small number of candidate genes using established islet cultures and new mouse models in order to characterise the effect they have on islet cell biology and tumorigenesis.
Increasing Appropriate Screening For Colorectal Cancer Patients And First Degree Relatives. A RCT.
Funder
National Health and Medical Research Council
Funding Amount
$1,372,866.00
Summary
Adoption of guideline recommendations is difficult to achieve. This research aims to improve adherence to guideline recommendations for surveillance for people with colorectal cancer and screening in their first degree relatives using an educational intervention. People with colorectal cancer and their first degree relatives will be randomly assigned to an educational intervention or to usual care, and adherence to guideline recommendations will be compared between groups.
Investigating The Role Of The NR4A Nuclear Receptor Family In Melanocyte Function And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Individuals with red hair and fair skin have a considerably greater risk of developing melanoma and non-melanoma skin cancer. Understanding the relationship that genes such as MC1R and NR4As have to skin functions such as tanning and protection from UV damage, will provide a greater insight into melanoma susceptibility and progression. Furthermore, understanding the role that abnormal NR4A regulation plays in melanoma formation will aid in the identification of new therapeutic targets.
Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects which contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear which are the most critical molecules ....Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects which contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear which are the most critical molecules contributing to this disease and thus which are the best targets for therapeutic intervention. In this proposal, we aim to study two molecules. The first is called BRCA1 and is particularly important in inherited susceptibility to breast cancer. The second is called PML and, although originally described as a leukaemia-associated gene, it has since been implicated in a number of cancers. Specifically, we aim to investigate the possibility that PML and BRCA1 work together to protect against cancer and that they do this by regulating the ends of chromosomes, that is, the telomeres.Read moreRead less