Molecular epidemiology of Barretts esophagus and cancer

Summary

Principal Investigator: D C Whiteman
Abstract: [unreadable] DESCRIPTION (provided by applicant): The incidence of adenocarcinoma (AC) of the esophagus has increased rapidly in most countries during the past three decades, yet the reasons are not well understood. AC typically arises on a background of Barrett's esophagus (BE). At the population level, relatively little is known about the environmental and genetic causes of BE and AC, or about factors which modify the natural history of BE to cause progression to cancer. In this population-based study, we aim to quantify the risks associated with exposure to epidemiologic and genetic risk factors for reflux esophagitis (RE), BE and AC. In parallel biospecimen analyses, we aim to identify molecular subtypes of BE and AC using microarray gene expression profiling and tissue arrays. To accomplish these aims, we will sample representative groups of patients with biopsyproven RE [n=400], BE [n=700] or AC [n=300] from all pathology laboratories servicing the target populations during a 3 year period, and compare them with two groups of controls. A representative group of population controls [n=600] will be sampled from a compulsory electoral register, and a group of biopsynegative tissue controls [n=400] will be sampled from the pathology laboratories. Cases and controls will answer identical questionnaires, focusing on gastro-intestinal symptoms, exposure to medications (especially reflux promoters, NSAIDs, COX-2 inhibitors, hormones), as well as smoking, alcohol, infection with Helicobacter pylori and family history of cancer. Blood samples will be collected from participants to identify genotypes associated with predisposition to RE, BE and AC. From cases and tissue controls, we will obtain specimens of biopsy or surgical tissue with the aim of determining the prevalence of molecular subtypes of BE and AC. Fresh tissue will be available from a proportion of clinic-based AC cases [n=50-100] for gene discovery through microarray gene expression profiling. From comprehensive mining of the expression profiling data we will identify diagnostic markers for the different subtypes of BE and AC, prognostic markers that predict likelihood of progression and/or response to therapy, and targets for rational drug design to treat BE and AC. Candidate genes will be validated in the paraffin sections available for all cases and tissue controls using tissue array technology. Epidemiologic analyses will then be performed comparing risks of exposure among the major disease groupings (RE, BE, AC), as well as for the molecular subtypes of RE, BE and AC. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]
Funding Period: 2002-09-27 - 2007-08-31
more information: NIH RePORT

Top Publications

  1. pmc Total body fat and the risk of Barrett's oesophagus - a bioelectrical impedance study
    Bradley J Kendall
    Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia School of Medicine University of Queensland, Brisbane, Australia Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia Electronic address
    Cancer Epidemiol 38:266-72. 2014
  2. pmc Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett's esophagus, and gastroesophageal reflux
    Weronica E Ek
    Affiliations of authors Statistical Genetics WEE, SM and Cancer Control Group DCW, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia WEE, SM Department of Biostatistics, University of Washington, Seattle, WA DML Department of Biosciences and Nutrition MD, FB, MZ Department of Medical Epidemiology and Biostatistics NLP, PKEM, Unit of Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery HN, and Department of Medical Epidemiology and Biostatistics WY, Karolinska Institutet, Stockholm, Sweden Gastrocentrum Medicin, Karolinska University Hospital, Stockholm, Sweden FB, PTS Division of Public Health Sciences LEO, TLV and Division of Human Biology BJR, Fred Hutchinson Cancer Research Center, Seattle, WA Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden HT Division of Gastroenterology and Hepatology YR, Department of Otolaryngology YR, and GI Outcomes Unit YR, Mayo Clinic, Rochester, MN Department of Epidemiology, MD Anderson Cancer Center, Houston, TX W HC Centre for Public Health, Department of Pediatrics
    J Natl Cancer Inst 105:1711-8. 2013
  3. ncbi Dietary antioxidants and risk of Barrett's esophagus and adenocarcinoma of the esophagus in an Australian population
    Torukiri I Ibiebele
    Population Health Department, Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia
    Int J Cancer 133:214-24. 2013
  4. pmc The risk of Barrett's esophagus associated with abdominal obesity in males and females
    Bradley J Kendall
    Cancer Program, Queensland Institute of Medical Research, Brisbane, QLD, Australia
    Int J Cancer 132:2192-9. 2013
  5. pmc A clinical risk prediction model for Barrett esophagus
    Aaron P Thrift
    Cancer Control Laboratory, Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia
    Cancer Prev Res (Phila) 5:1115-23. 2012
  6. pmc Cigarette smoking increases risk of Barrett's esophagus: an analysis of the Barrett's and Esophageal Adenocarcinoma Consortium
    Michael B Cook
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852 7234, USA
    Gastroenterology 142:744-53. 2012
  7. ncbi The use of nonsteroidal anti-inflammatory drugs and the risk of Barrett's oesophagus
    A P Thrift
    School of Population Health, The University of Queensland, Public Health Building, Herston, Brisbane, Australia
    Aliment Pharmacol Ther 34:1235-44. 2011
  8. pmc Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma
    Derek J Nancarrow
    Oncogenomics, Queensland Institute of Medical Research, Herston, Queensland, Australia
    PLoS ONE 6:e22513. 2011
  9. ncbi Lifetime alcohol consumption and risk of Barrett's Esophagus
    Aaron P Thrift
    School of Population Health, The University of Queensland, Brisbane, Australia
    Am J Gastroenterol 106:1220-30. 2011
  10. pmc High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population
    Torukiri I Ibiebele
    Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
    J Nutr 141:274-83. 2011

Scientific Experts

  • Derek J Nancarrow
  • Torukiri I Ibiebele
  • Michael B Cook
  • Kylie J Smith
  • David C Whiteman
  • Bradley J Kendall
  • Aaron P Thrift
  • Suzanne O'Brien
  • Nicholas K Hayward
  • Adele C Green
  • Penelope M Webb
  • Johannes B Prins
  • Graeme A Macdonald
  • Weronica E Ek
  • Thomas L Vaughan
  • Nirmala Pandeya
  • A P Thrift
  • Annika Antonsson
  • N Pandeya
  • A C Green
  • D C Whiteman
  • P M Webb
  • David M Purdie
  • Michael Connard
  • Linda Terry
  • Deborah Roffe
  • Peter G Parsons
  • David I Watson
  • B Mark Smithers
  • Andrew Clouston
  • David Gotley
  • B J Kendall
  • Helena Nordenstedt
  • Leslie Bernstein
  • Patrik K E Magnusson
  • Stuart Macgregor
  • Francesca Bresso
  • Tim D Spector
  • Laura J Hardie
  • Douglas A Corley
  • Mauro D'Amato
  • Yvonne Romero
  • Marco Zucchelli
  • David M Levine
  • Geoffrey Liu
  • Nancy L Pedersen
  • Marilie D Gammon
  • Nicholas J Shaheen
  • Wong Ho Chow
  • Hans Tornblom
  • Alan G Casson
  • Harvey A Risch
  • Liam J Murray
  • Pirro Hysi
  • Anna H Wu
  • Weimin Ye
  • Peter T Schmidt
  • Brian J Reid
  • Lynn E Onstad
  • Nigel C Bird
  • Kylie Ann Mallitt
  • Ian S Brown
  • Frances Walker
  • Ellen Minehan
  • Teresa Barnes
  • Janine Thomas
  • Troy Sadkowski
  • MaryRose Malt
  • Jo White
  • Sue O'Keefe
  • Paul A Drew
  • Ian Brown
  • Hayley Berry
  • Karen Harrap
  • Gabby Connor
  • Suzanne Lipshut
  • Leanne Bowes
  • Suzanne Moore
  • Lorelle Smith
  • Andrea McMurtrie
  • I Brown
  • Glyn G Jamieson
  • N Walker
  • Paul Drew
  • Marian Martin
  • Sandra J Pavey
  • G A Macdonald
  • J B Prins
  • N K Hayward

Detail Information

Publications16

  1. pmc Total body fat and the risk of Barrett's oesophagus - a bioelectrical impedance study
    Bradley J Kendall
    Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia School of Medicine University of Queensland, Brisbane, Australia Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia Electronic address
    Cancer Epidemiol 38:266-72. 2014
    ..We aimed to quantify the association between total body fat (measured by bioelectrical impedance) and risk of BO and examine if this association was modified by gastro-oesophageal reflux (GOR) and abdominal obesity...
  2. pmc Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett's esophagus, and gastroesophageal reflux
    Weronica E Ek
    Affiliations of authors Statistical Genetics WEE, SM and Cancer Control Group DCW, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia WEE, SM Department of Biostatistics, University of Washington, Seattle, WA DML Department of Biosciences and Nutrition MD, FB, MZ Department of Medical Epidemiology and Biostatistics NLP, PKEM, Unit of Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery HN, and Department of Medical Epidemiology and Biostatistics WY, Karolinska Institutet, Stockholm, Sweden Gastrocentrum Medicin, Karolinska University Hospital, Stockholm, Sweden FB, PTS Division of Public Health Sciences LEO, TLV and Division of Human Biology BJR, Fred Hutchinson Cancer Research Center, Seattle, WA Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden HT Division of Gastroenterology and Hepatology YR, Department of Otolaryngology YR, and GI Outcomes Unit YR, Mayo Clinic, Rochester, MN Department of Epidemiology, MD Anderson Cancer Center, Houston, TX W HC Centre for Public Health, Department of Pediatrics
    J Natl Cancer Inst 105:1711-8. 2013
    ..Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA...
  3. ncbi Dietary antioxidants and risk of Barrett's esophagus and adenocarcinoma of the esophagus in an Australian population
    Torukiri I Ibiebele
    Population Health Department, Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia
    Int J Cancer 133:214-24. 2013
    ..However, our data suggest that a high intake of β-carotene may be associated with decreased risk of dysplastic BE...
  4. pmc The risk of Barrett's esophagus associated with abdominal obesity in males and females
    Bradley J Kendall
    Cancer Program, Queensland Institute of Medical Research, Brisbane, QLD, Australia
    Int J Cancer 132:2192-9. 2013
    ..The power to detect differences between sexes in the risk of BE associated with abdominal obesity was limited by the number of females in the study...
  5. pmc A clinical risk prediction model for Barrett esophagus
    Aaron P Thrift
    Cancer Control Laboratory, Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia
    Cancer Prev Res (Phila) 5:1115-23. 2012
    ..The prediction model performed reasonably well and has the potential to be an effective and useful clinical tool in selecting patients with gastroesophageal reflux symptoms to refer for endoscopic screening for Barrett esophagus...
  6. pmc Cigarette smoking increases risk of Barrett's esophagus: an analysis of the Barrett's and Esophageal Adenocarcinoma Consortium
    Michael B Cook
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852 7234, USA
    Gastroenterology 142:744-53. 2012
    ..We investigated whether tobacco smoking and other factors increase risk for Barrett's esophagus...
  7. ncbi The use of nonsteroidal anti-inflammatory drugs and the risk of Barrett's oesophagus
    A P Thrift
    School of Population Health, The University of Queensland, Public Health Building, Herston, Brisbane, Australia
    Aliment Pharmacol Ther 34:1235-44. 2011
    ....
  8. pmc Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma
    Derek J Nancarrow
    Oncogenomics, Queensland Institute of Medical Research, Herston, Queensland, Australia
    PLoS ONE 6:e22513. 2011
    ..While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC...
  9. ncbi Lifetime alcohol consumption and risk of Barrett's Esophagus
    Aaron P Thrift
    School of Population Health, The University of Queensland, Brisbane, Australia
    Am J Gastroenterol 106:1220-30. 2011
    ..However, few studies have investigated this association and findings have been inconsistent. We sought to examine the association between measures of total and beverage-specific alcohol consumption and BE risk...
  10. pmc High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population
    Torukiri I Ibiebele
    Queensland Institute of Medical Research, Genetics and Population Health Division, Herston, Brisbane, Australia
    J Nutr 141:274-83. 2011
    ..High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC...
  11. ncbi High-risk human papillomavirus in esophageal squamous cell carcinoma
    Annika Antonsson
    Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4029, Australia
    Cancer Epidemiol Biomarkers Prev 19:2080-7. 2010
    ....
  12. ncbi Current and past smoking significantly increase risk for Barrett's esophagus
    Kylie J Smith
    Division of Population Studies and Human Genetics, Queensland Institute of Medical Research, Brisbane, Australia
    Clin Gastroenterol Hepatol 7:840-8. 2009
    ..However, few population-based studies of BE have been conducted, so little is known about potentially modifiable causes of this disease...
  13. ncbi Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays
    Derek J Nancarrow
    Oncogenomics, Queensland Institute of Medical Research, Herston, Queensland, Australia
    Cancer Res 68:4163-72. 2008
    ..The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development...
  14. ncbi Leptin and the risk of Barrett's oesophagus
    B J Kendall
    Division of Population Studies and Human Genetics, Queensland Institute of Medical Research, Brisbane, Australia
    Gut 57:448-54. 2008
    ....
  15. pmc SiDCoN: a tool to aid scoring of DNA copy number changes in SNP chip data
    Derek J Nancarrow
    Oncogenomics, Queensland Institute of Medical Research, Herston, Queensland, Australia
    PLoS ONE 2:e1093. 2007
    ..We believe this tool will prove useful to others working in the area, both as a training tool, and to aid in the interpretation of complex copy number changes...
  16. pmc Interactions among smoking, obesity, and symptoms of acid reflux in Barrett's esophagus
    Kylie J Smith
    Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Queensland 4029, Australia
    Cancer Epidemiol Biomarkers Prev 14:2481-6. 2005
    ..Clinical studies suggest acid reflux causes Barrett's esophagus; however, no population-based estimates of risk have been reported, and the role of other health factors in modifying risk is unclear...