Cancer Control Group - project details

Cancer imposes a major health burden in most human populations. In Australia, almost one in three deaths is due to cancer, and this proportion will rise as the population ages.

Research undertaken by our group is conducted with a view to reducing the burden of cancer through successfully translating research findings into policy and practice. This includes research to identify the environmental and genetic factors that cause cancer, as well as research into early diagnosis, treatment and survival. Our research has focused primarily on melanoma and cancers of the skin, and more recently on cancers of the digestive tract. The latter includes major national population-based case-control studies of oesophageal cancer and Barrett's oesophagus (a pre-cancerous condition).

Exploring the causal pathways to cutaneous melanoma

Melanomas are cancers arising from the pigment cells of the skin, and are among the most commonly occurring cancers in this country. Each year, more than 8,000 Australians are diagnosed with invasive melanoma, resulting in some 900 deaths annually. Sunlight is the principal factor which causes this disease, although there is increasing evidence that the role of sunlight in causing melanoma is not the same for all people who develop this disease. A new hypothesis proposes that the malignant course of melanomas may reflect their causal origins, with melanomas induced by chronic sunlight exposure perhaps being more aggressive than other melanomas. We will undertake a large study of patients with melanoma to investigate both the causal pathways and their influence on markers of tumour aggressiveness. We will capture detailed information about the microscopic appearance of the melanomas from pathologists at the time of diagnosis, and marry this to the information reported by the patients about their past history of sun exposure. When complete, this study will provide new information about the causes of melanoma. Such knowledge is crucial to controlling and preventing this cancer.

Case-control study of genetic and environmental risk factors for pancreatic carcinoma

Pancreatic cancer is the fourth most common cause of cancer death in developed countries. The causes remain largely unknown. This Queensland-based case-control study is collecting questionnaire information and blood samples from men and women newly diagnosed with pancreatic cancer and a similar number of cancer-free controls. The aims of the study are to examine environmental causes of pancreatic ductal carcinoma and their possible interaction with genes that might determine susceptibility. Over 200 people with pancreatic cancer have now been interviewed and recruitment will continue until July 2011.

Coeliac disease as a risk factor for squamous cell carcinoma of the oesophagus

Funded by Gallipolli Research Foundation

B Kendall (QIMR/Princess Alexandra Hospital), D Whiteman, G Macdonald (UQ/ Princess Alexandra Hospital)

Coeliac disease (CD) is an immune mediated condition in which inflammation and atrophy of the small intestine occur when genetically predisposed individuals are exposed to dietary gluten. Until recent times, diagnosis of the condition could only be made with an endoscopic small bowel biopsy and the majority of patients diagnosed with the condition had clinical manifestations of the villous atrophy. Recently, serological tests have been developed for the diagnosis of CD. Use of these tests in population studies has shown a much higher prevalence of the condition than previously appreciated. A study from Denmark showed an increase prevalence of CD from 1 in 10,000 pre serology to 1 in 300 with the assay. Multiple serological tests have been developed for the diagnosis of CD with IgA anti-TTG being widely used because of its high sensitivity and specificity. Approximately 2% of those with CD and 0.5% of the general population are IgA deficient. In those cases of IgA deficiency, IgG anti-gliadin antibodies can be used to screen for CD  Cohort studies have shown that people with coeliac disease have increased risk of cancer. The majority of this risk was related to lymphoma and lymphoproliferative disorders, but a number of studies have suggested an increased risk of gastrointestinal cancers including Oesophageal SCC in those with CD. To date, no case-control studies have been published examining the relationship between coeliac disease and oesophageal SCC. As custodians of the largest collection of annotated oesophageal SCC serum specimens in the industrialised world, we are well-placed to test this hypothesis definitively. If CD is identified as a significant risk factor for Oesophageal SCC, this has potential future implications in terms of population screening for CD, surveillance of those with CD and understanding of the pathogenesis of this terrible disease.

PROBE-NET: The Progression of Barrett's Oesophagus to Cancer Network

Funded by Cancer Council NSW and NHMRC

D Whiteman (QIMR), R Lord (St Vincents, NSW), D Watson (Flinder Medical Centre, SA), W Phillips (Peter MacCallum Cancer Centre, VIC), N Hayward (QIMR)

We have established a consortium to develop a nationwide resource for the study of Barrett's oesophagus. Patients with oesophageal reflux, metaplasia and neoplasia will be recruited from around the country to participate in this ongoing project. The resource will be used for current and future studies of cancer, particularly with a view to developing new diagnostic and screening tests for these conditions.

BEAGESS: Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study

We are undertaking a large-scale genome-wide association study (GWAS) which takes advantage of the extensive data collected by investigators in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), representing virtually all of the high-quality population-based and other epidemiologic studies of BE and EA in the world. The overall goal of our research is to evaluate the influence of genetic susceptibility on risk of EA and its main precancerous condition, BE. The primary aims are to identify the genetic polymorphisms most strongly associated with risk of these conditions. In secondary aims we will evaluate the extent to which the most significant associations vary according to key environmental and host risk factors for these conditions, including gender, obesity and cigarette smoking. These results will guide additional exploratory analyses examining ways in which individual SNP results might be aggregated to shed light on the importance of specific pathways relevant to the etiology of BE and EA, and to identify possible epistatic effects.

BEACON: The Barrett's Oesophagus and Adenocarcinoma Consortium

BEACON is an international collaborative group established by the US National Cancer Institute to promote research into oesophageal cancer. The ACS and SDH studies were invited as founding members of the group.

Tom Vaughan MD - Fred Hutchinson Cancer Research Center, Seattle Brian Reid MD PhD - Fred Hutchinson Cancer Research Center, Seattle Olof Nyren MD PhD - Karolinska Institute, Stockholm Jesper Lagergren MD PhD - Karolinska Institute, Stockholm Weimin Ye MD PhD - Karolinska Institute, Stockholm Marilie Gammon PhD - University of North Carolina Nick Shaheen MD MPH - University of North Carolina Anna Wu PhD - University of Southern California Lesley Bernstein PhD - University of Southern California Doug Corley MD PhD - Kaiser Permanente, San Francisco Liam Murray MBBS PhD - Queens University, Belfast Chris Wild PhD - Leeds University David Forman PhD - Leeds University Alan Casson FRCS PhD - University of Saskatchewan, Canada David Whiteman MBBS PhD - Queensland Institute of Medical Research Funded by US National Cancer Institute R01 CA136725-01A1

Centre for Research Excellence in Sun and Health (funded by National Health and Medical Research Council of Australia)

M Kimlin, Queensland University of Technology, D Whiteman, Queensland Institute of Medical Research, R Lucas, Australian National University, C Sinclair, Cancer Council Victoria, R Neale, Queensland Institute of Medical Research, P Ebeling, University of Melbourne, P Youl, Cancer Council Queensland, L Gordon, Queensland Institute of Medical Research, M Janda, Queensland University of Technology

The Centre for Research Excellence in Sun and Health (CRESH) will build an evidence base leading to the development of Australian public health guidelines to balance the adverse and beneficial effects of sun exposure to optimise the health of the Australian community.