Integrating Epidemiological and Genomic Factors to Inform Outcomes in Barrett’s Oesophagus and Oesophageal Adenocarcinoma
type: CreativeWork
description: The incidence of oesophageal adenocarcinoma (OAC) has rapidly increased, and its prognosis remains poor. Barrett’s oesophagus (BO) is considered the precursor to OAC, however, BO is not apparent adjacent to tumour in nearly half of OAC patients. We have previously demonstrated that patients with BO-adjacent tumours (BO+ve OAC phenotype) have a favourable prognosis compared to those without evidence of BO adjacent to the tumour (BO-ve OAC phenotype). It has been suggested that the BO-ve OAC tumour phenotype may arise independently of BO. Recent experimental and computational studies show that all OACs likely arise from BO, even if this precursor lesion is not histologically apparent adjacent to the tumour. However, there is a lack of consolidated clinical, epidemiological and molecular data to examine this question. In this thesis, I used orthogonal approaches to examine the overlap between the BO+ve OAC and BO-ve OAC phenotypes and explain the aetiology and the observed altered prognosis. To achieve this, I assembled a large cohort (n=4,695) comprising BO+ve OAC cases (n=1,235), BO-ve OAC cases (n= 880), OAC cases with an unascertainable BO status (BO(?) OAC; n= 985), cancer-free BO cases (n=1,091) and reflux controls (n=554). A subset of the OAC cases (n=950) with available clinical, epidemiological and whole-genome sequencing data was also examined. There was little to no association between most of the 34 clinical and epidemiological factors and the OAC phenotypes. Weak associations were observed for cigarette smoking and gender with self-reported ever-smoking and female cases being more likely in the BO-ve OAC phenotype group relative to the BO+ve OAC phenotype group. However, tumour stage, lymph node spread and metastasis (TNM) was strongly associated with increased risk of BO-ve OAC. Higher TNM stage was strongly correlated with BO-ve OAC with an adjusted odds ratio of 2.4 (95\% CI:1.8-3.3), 2.9 (95\% CI:2.2-3.9) and 3.2 (95\% CI: 1.7-5.9) for stages II, III a…
abstract: The incidence of oesophageal adenocarcinoma (OAC) has rapidly increased, and its prognosis remains poor. Barrett’s oesophagus (BO) is considered the precursor to OAC, however, BO is not apparent adjacent to tumour in nearly half of OAC patients. We have previously demonstrated that patients with BO-adjacent tumours (BO+ve OAC phenotype) have a favourable prognosis compared to those without evidence of BO adjacent to the tumour (BO-ve OAC phenotype). It has been suggested that the BO-ve OAC tumour phenotype may arise independently of BO. Recent experimental and computational studies show that all OACs likely arise from BO, even if this precursor lesion is not histologically apparent adjacent to the tumour. However, there is a lack of consolidated clinical, epidemiological and molecular data to examine this question. In this thesis, I used orthogonal approaches to examine the overlap between the BO+ve OAC and BO-ve OAC phenotypes and explain the aetiology and the observed altered prognosis. To achieve this, I assembled a large cohort (n=4,695) comprising BO+ve OAC cases (n=1,235), BO-ve OAC cases (n= 880), OAC cases with an unascertainable BO status (BO(?) OAC; n= 985), cancer-free BO cases (n=1,091) and reflux controls (n=554). A subset of the OAC cases (n=950) with available clinical, epidemiological and whole-genome sequencing data was also examined. There was little to no association between most of the 34 clinical and epidemiological factors and the OAC phenotypes. Weak associations were observed for cigarette smoking and gender with self-reported ever-smoking and female cases being more likely in the BO-ve OAC phenotype group relative to the BO+ve OAC phenotype group. However, tumour stage, lymph node spread and metastasis (TNM) was strongly associated with increased risk of BO-ve OAC. Higher TNM stage was strongly correlated with BO-ve OAC with an adjusted odds ratio of 2.4 (95\% CI:1.8-3.3), 2.9 (95\% CI:2.2-3.9) and 3.2 (95\% CI: 1.7-5.9) for stages II, III a…
author: Zamani, Shahriar
language: eng
keywords: Barrett's oesophagus, Epidemiology, Molecular epidemiology, Oesophageal cancer, Public health
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/8e75b657-6065-4eda-b2f0-2014e9fda2fa/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-04-14
date modified: 2026-07-22T22:24:13Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.96926