Liam Murray Cancer Epidemiology and Prevention Research Group Queen’s University Belfast Dublin September 3 rd 2009 The Northern Ireland Barrett’s Register: incidence and risk factors for progression to cancer

What is Barrett’s oesophagus? Shaheen NJ, Richter JE. Lancet 2009;373:

Why is Barrett’s oesophagus important?

OAC trends by sex and deprivation category, England and Wales, 1986–2001 The American Journal of Gastroenterology (2008) 103, 2694–2699

Trends in Barrett’s oesophagus - USA Conio et al Gut 2001;48:

Copyright ©2009 BMJ Publishing Group Ltd. Corley, D A et al. Gut 2009;58: Recent trends in Barrett's oesophagus diagnosis in the USA

Copyright ©2009 BMJ Publishing Group Ltd. Corley, D A et al. Gut 2009;58: Recent trends in Barrett's oesophagus prevalence in the USA

Cancer risk in Barrett's oesophagus by study size

Rationale for the Northern Ireland Barrett’s Register Substantial increase in rate of diagnosis of BO Very large increases in prevalence of diagnosed BO Lack of clarity on cancer risk effectiveness/cost-effectiveness of endoscopic surveillance? Groups at high risk of progression are not well established Biomarkers for progression have not been identified Very limited investigation of the factors associated with progression to cancer any modifiable lifestyle factors? How should BO patients be managed? What advice can Barrett’s patients be given?

The Northern Ireland Barrett’s Register ( ) All oesophageal biopsy specimens from NI hospitals Biopsy at OGJ Columnar Epithelium of oesophagus No Columnar Epithelium SIM present Unclassified Deaths Incident cancers & HGD Not present Manual review of path reports Individual patients identified Note review / Pathology review Linkage to Cancer Registry / Death files Malignancy

Prevalence of BO diagnosis in Northern Ireland

The Northern Ireland Barrett’s Register: follow-up data

Incidence of OAC in Barrett’s oesophagus Patient Characteristics Number of patients (pyr), total events Incidence of events (per 1,000 pyr) oesophageal cancer oesophageal and gastric cardia cancer oesophageal cancer and HGD oesophageal/ gastric cardia cancer and HGD All patients7585 (38076), ( )1.8 ( )2.0 ( )2.4 ( ) SIM at index biopsy Present3533 (18901), ( )2.9 ( )3.3 ( )3.9 ( ) Absent2865 (15072), ( )0.7 ( )0.6 ( ( ) Unknown1187 (4103), 51.0 ( )1.2 ( )1.0 ( )1.2 ( ) Age at diagnosis < (10675), ( )0.7 ( )0.9 ( )1.1 ( ) (8610), ( )1.5 ( )1.7 ( )2.2 ( ) (8897), ( )3.1 ( )3.0 ( )3.8 ( ) (7171), ( )2.0 ( )2.1 ( )2.2 ( ) (2733), 72.2 ( ) 2.6 ( )

?Subgroups at high risk of progression from BO to OAC: Gender Incidence of events per 1,000 pyr Number of patients (pyr), total events oesophageal cancer oesophageal and gastric cardia cancer oesophageal cancer and HGD oesophageal/ gastric cardia cancer and HGD Male 4413 (21949), ( )2.4 ( )2.7 ( ( ) Female 3172 (16127), ( )1.1 ( ) 1.4 ( ) Patients with endoscopically visible segment and SIM on histology Male 1582 (8423), ( )3.0 ( )4.2 ( )4.5 ( ) Female 906 (4844), ( )2.9 ( )2.7 ( )3.5 ( ) The Northern Ireland Barrett’s Register

?Subgroups at high risk of progression from BO to OAC: Length of segment and dysplasia Patient Characteristics Number of patients (pyr), total events Incidence of events per 1,000 pyr oesophageal cancer oesophageal and gastric cardia cancer oesophageal cancer and HGD oesophageal/ gastric cardia cancer and HGD All patients 2488 (13267), ( )2.9 ( )3.6 ( )4.1 ( ) Length of BO Long 960 (5759), ( )3.8 ( )4.5 ( )5.2 ( ) Short 289 (1286), 30 (0-2.8) 2.3 ( ) Length unknown 1239 (6222), ( )2.7 ( )3.1 ( )3.5 ( ) Dysplasia No 2136 (11253), ( )2.2 ( )2.8 ( )3.1 ( ) Low grade 182 (1032),138.8 ( )9.8 ( )11.7 ( ) 12.7 ( ) Unknown 170 (990), 52.0 ( )4.0 ( )3.0 ( )5.0 ( ) Patients with endoscopically visible segment and SIM on histology The Northern Ireland Barrett’s Register

Clinical factors associated with progression to OAC: interim results of the case note review Factor Well-defined BO group HR (95% CI)P value Reflux symptoms at referral No Unknown Yes 257 (23.5) 153 (13.9) 685 (62.6) ( ) 0.5 ( ) Markers of oesophageal inflammation No/unknown Yes 563 (51.4) 532 (48.6) ( )0.01 PPIs No Yes 150 (13.7) 945 (86.3) (1.1—11.6)0.03 H 2 antagonists No Yes 833 (76.1) 262 (23.9) ( )0.02 Aspirin No Yes 973 (88.9) 122 (11.1) ( )0.24 NSAIDs No Yes 1034 (94.4) 61 (5.6) ( )0.72 H. pylori eradication therapy No Yes 887 (81.0) 208 (19.0) ( )0.56

Lifestyle factors associated with progression to OAC Factor Well-defined BO group HR (95% CI)P value BMI <25 25-<30 30 or more Unknown 78 (7.1) 123 (11.2) 69 (6.3) 825 (75.3) ( ) 0.7 ( ) 0.6 ( ) Weight 1 st quartile 2 nd quartile 3 rd quartile 4 th quartile Unknown 168 (15.3) 180 (16.4) 177 (16.2) 185 (16.9) 385 (35.2) ( ) 1.8 ( ) 1.4 ( ) 2.6 ( ) Smoking Never Ex-smoker Current Unknown 471 (43.0) 232 (21.2) 256 (23.4) 136 (12.4) ( ) 0.6 ( ) 0.3 ( ) Alcohol None <10 units/wk units/wk >20 units/wk Unknown 337 (30.8) 317 (28.9) 149 (13.6) 71 (6.5) 221 (20.2) ( ) 1.0 ( ) 4.3 ( ) 3.7 ( )

Conclusions Confirm a low risk of progression to cancer/HGD Groups at higher risk long segment BO dysplasia at baseline age at baseline Rate of progression similar in men and women Oesophageal inflammation at diagnosis associated with increased risk of progression? No lifestyle risk factors for progression identified Inadequate data from case note review Prospective cohorts of BO required

Northern Ireland Barrett’s Register: Investigators and funders Prof Liam Murray, CEPRG/NICR, QUB Dr Brian Johnston, Belfast HSCT Dr Anna Gavin, NICR, QUB Dr Damian McManus, Belfast HSCT Dr Helen Mulholland, CEPRG Dr Lesley Anderson, CEPRG Dr Shivaram Bhat, CEPRG Collaborators Dr Laura Hardie, Leeds University Dr Rebecca Fitzgerald, University of Cambridge Dr Lawrence Lovat, UCLH Prof Marco Novelli, UCLH Clerical staff Kate Donnelly (Data abstractor) Rosemary Ward (Data abstractor) Ulster Cancer Foundation