Oesophageal Cancer and pre-cancer

Molecular epidemiology of oesophageal cancer: The Australian Cancer Study

Molecular Epidemiology of Barrett's Oesophagus: The Study of Digestive Health

Towards prognostic markers for oesophageal cancer: The ACS Clinical Follow-Up Study

Clinical measures of obesity and risk of Barrett's oesophagus: The Barrett's Oesophagus Metabolic Study

Coeliac disease as a risk factor for Squamous Cell Carcinoma of the Oesophagus

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

BEACON: The Barrett's Oesophagus and Adenocarcinoma Consortium

Molecular epidemiology of oesophageal Cancer: The Australian Cancer Study
D Whiteman, A Green, P Webb, P Parsons, N Hayward
There are two types of cancer of the oesophagus: squamous cell cancer and adenocarcinoma. In Western countries, the rates of adenocarcinoma of the oesophagus are rising more rapidly than any other cancer. To explore the environmental and genetic causes of cancers of the oesophagus, we conducted a population-based case-control study recruiting newly diagnosed patients throughout Australia between 2002 and 2005. We enrolled 367 patients with adenocarcinoma of the oesophagus, 426 patients with adenocarcinoma of the gastroesophageal junction, 309 patients with squamous cell cancer and compared them to 1580 people without cancer for factors including their height and weight, smoking, alcohol, diet, medications and past medical history. We have shown that obesity is a major risk factor for adenocarcinoma of the oesophagus, and that it interacts with acid reflux to greatly increase a person's risk of cancer. Other published findings are that frequent use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) greatly reduce the risk of all types of oesophageal cancer, and that the different types of oesophageal cancer are associated with smoking in substantially different ways (a finding of importance for prevention). We have identified a number of DNA repair genes that appear to increase the risk of adenocarcinoma of the oesophagus, and we are continuing to explore associations with a number of other factors. Data from this study is contributing to the international BEACON collaboration.

Molecular Epidemiology of Barrett's Oesophagus: The Study of Digestive Health
Funded by the US National Cancer Institute 2002-2007
D Whiteman, P Webb, A Green, N Hayward, P Parsons, S Pavey in collaboration with P Drew (Flinders University), D Gotley (University of Queensland), G Jamieson, D Purdie, B Smithers (University of Queensland), D Watson (Flinders University)
Nearly all adenocarcinomas of the oesophagus arise from a pre-cancerous condition called Barrett's oesophagus. This condition is becoming increasingly prevalent, yet relatively little is known about its causes or its natural history. We have been exploring the environmental and genetic causes of Barrett's oesophagus through a population-based case-control study recruiting newly diagnosed patients in Queensland and South Australian between 2003 and 2006. We enrolled 479 patients with Barrett's oesophagus and compared them to 646 people without Barrett's oesophagus for factors including their height and weight, smoking, alcohol, diet, medications and past medical history. Using this rich resource, we have shown that leptin (a hormone secreted by fat cells) is significantly higher in men with Barrett's oesophagus than controls, even after accounting for related factors such as obesity. Further analyses will continue through 2008-9.

Towards prognostic markers for oesophageal cancer: The ACS Clinical Follow-Up Study
Funded by the National Health and Medical Research Council 2006-2008
D Whiteman, A Green, N Hayward in collaboration with D Gotley & BM Smithers (University of Queensland), D Watson (Flinders University), G Falk (Concord Hospital), G Smith (Royal North Shore Hospital), G Kiroff (Barwon Surgical, Geelong), A Clouston (Histopath, Sydney)
Until recently, cancer of the oesophagus was a very uncommon tumour in Australia and other western populations. However during the past three decades, there have been very large increases in the incidence of this disease. Unfortunately, treatment options are limited, survival is often short, and there is no way of identifying which tumours will respond to therapy. This study will collect treatment and health outcomes data for a population-based cohort of patients with oesophageal cancer. The goal is to identify prognostic and predictive markers to aid patients and clinicians when making treatment decisions, as now exist for breast cancer. Such markers may also serve as novel targets for therapy. The proposed study builds upon the platform of the Australian Cancer Study [ACS], one of the world's largest studies of oesophageal cancer.

Clinical measures of obesity and risk of Barrett's oesophagus: The Barrett's Oesophagus Metabolic Study
Funded by the Queensland Cancer Fund 2007-2008
D Whiteman, B Kendall, G Macdonald (Princess Alexandra Hospital)
We have shown that obesity is likely to be a major risk factor for Barrett's oesophagus and oesophageal adenocarcinoma, but how it confers increased risk is unknown. With the high prevalence of obesity in the Australian population, and with predictions of an impending obesity epidemic, we need to identify how increased levels of body fat induce these conditions so that this knowledge can be used for prevention. By comparing patients with proven Barrett's oesophagus to healthy people selected from the general population, we aim to investigate the link between obesity and Barrett's oesophagus. In particular, we will investigate the role of certain hormones (including insulin) that are known to be affected by obesity. Once we have identified those factors, we can then investigate ways of counteracting them with the goal of preventing the development of Barrett's oesophagus and subsequent cancer.

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
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.

BEACON: The Barrett's Oesophagus and Adenocarcinoma Consortium
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

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