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About Sarcomas and our research objective

Sarcomas are uncommon cancers that disproportionately affect young people, with a high mortality and devastating consequences of treatment. Collectively, these features lead to a community impact equivalent or greater than more common cancers, such as cervical cancer, or head and neck cancer.

Cancer is a genetic disease. It is vital that we understand genetic risk factors in sarcoma, because

  • the mutated (faulty) gene can be transmitted to the next generation. Many young patients face decisions regarding having a family, and effective strategies exist for antenatal diagnosis;
  • these individuals carry a high risk of subsequent malignancy (as high as one in five);
  • being able to advise whether a family member also carries cancer-causing genes is very important to advise appropriate screening programmes;
  • a thorough understanding of cancer-causing genes is the basis for developing new treatments for sarcomas.

Clinical genetic counselling for an increased risk of most adult sarcomas is difficult, because existing studies about the hereditary basis of sarcoma are extremely limited. Moreover, up to a third of young people with proven genetic mutations lack a striking family history. In early onset breast cancer approximately 60% of all identified mutations were reported to occur in patients without family history. Current information, based on referral to familial cancer registries that by definition necessitates a significant family history of the disease, will not help identify these cases, so the true incidence and natural history of ‘new’ genetic mutations causing a risk of sarcoma in subsequent generations is simply not known.

We believe that a population-based strategy anchored in adult sarcoma setting, will generate important insights into the genetic basis and clinical risks of adult-onset sarcoma.

Specific Aims

  • Establishment of an Australian registry for sarcoma kindreds, collaborating with existing international registries, as a clinical and research resource. This registry will utilize the clinical ‘front end’ of the Australasian Sarcoma Study Group, the familial cancer genetics infrastructure of kConFab, the molecular resources of the Peter MacCallum Centre for Cancer Genomics and Predictive Medicine, the Genetic Epidemiology Unit of the University of Melbourne, and the Queensland Institute of Medical Research
  • Development of clinically useful, population-based criteria for stratifying genetic or hereditary risk for adult-onset sarcoma.

Strategy

We will recruit 400 new cases of sarcoma over a three year period, along with 400 ‘control’ patients. In each case in addition to a detailed standard clinical dataset, a detailed family history and history of sarcoma-specific risk factors will be taken. Consent will be obtained for sampling of blood and tumour tissue (where available) for research purposes, as well as for contacting patients again in the event of discovery of important information. This information will be stored in a dedicated cancer genetics database. Biospecimens will be stored in dedicated biobank at Peter MacCallum.

Researchers will be able to apply to a central access committee to use these samples for specific research projects. Based on the experience of kConFab (see below), the infrastructure created above will provide an invaluable resource for scientists, who will undertake research studies into the genetic basis of adult onset sarcoma and the development of novel therapies for this group of malignancies funded by competitive peer-reviewed processes (National Health and Medical Research Council, Cancer Councils, etc).

kConFab

kConFab, founded by philanthropic vision, brings together geneticists, clinicians, surgeons, genetic counsellors, psychosocial researchers, pathologists and epidemiologists from all over Australia and New Zealand who believe the causes and consequences of familial predisposition to breast cancer can be understood only by a concerted national effort at both the basic and clinical level.

In 1997, kConFab, with the help of the Family Cancer Centres in Australia and New Zealand began enrolling families with a strong history of breast and breast/ovarian cancer. Genetic, epidemiological, medical and psychosocial data collected from these families by kConFab nurses and researchers are stored in a de-identified fashion in a central relational database. Biospecimens collected from family members are used to characterise germ-line mutations in predisposing genes such as BRCA1 and BRCA2. kConFab has accumulated data on more than 1100 multigenerational, multicase kindreds.

kConFab itself is not a research organisation in the usual sense, but rather provides a resource upon which researchers can draw. The aims of the consortium are to make data and biospecimens widely available to researchers for use in peer-reviewed, ethically-approved funded research projects on familial aspects of breast cancer. At present, kConFab is supplying biological specimens and data to more than 30 research projects world wide resulting in 54 scientific publications to date.

We will use the established kConFab national infrastructure of research nurses and associated laboratories to ascertain and recruit individuals and families with adult onset sarcoma. We will adopt the kConFab database and tissue banking protocols and consequently the registry will be established quickly and run efficiently as these processes are already established for a similar study for familial breast cancer.

We will collaborate with Professor John Hopper at the University of Melbourne to characterize the pedigree data from this clinical set to classify sarcoma and other cancer risks according to patterns of family pedigrees. This will provide an immediately useful resource for Doctors treating sarcoma patients, who currently have little information on which to provide useful clinical advice to other family members. It will also be possible to compare these to existing registries where sarcoma has been identified primarily through a diagnosis of breast or colorectal cancer.

Significance

The proposed study is innovative and internationally significant because

  • Australia has an enviable reputation for national population-based familial cancer studies, exemplified by kConFab
  • it draws together the clinical resources of the Australasian Sarcoma Study Group
  • has outstanding international collaborators and linkages.

The ASK study will provide clinically useful information, facilitate basic research in this area, and become an enduring resource for geneticists and sarcoma biologists nationally and internationally.