Biomarkers in Barrett's oesophagus

2010 ◽  
Vol 38 (2) ◽  
pp. 343-347 ◽  
Author(s):  
Qizhi Huang ◽  
Laura J. Hardie
Keyword(s):  
Disease Diagnosis ◽  
Population Based ◽  
Response To Therapy ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Therapeutic Success ◽  
Double Blind ◽  
Barrett's Oesophagus ◽  
Molecular Features ◽  
Alternative Sources

Biomarkers are needed to screen multiple stages in the clinical pathway of Barrett's oesophagus patients; from disease diagnosis to risk stratification and predicting response to therapy. Routes to the identification of biomarkers have been recognized by known molecular features of the disease and more recently through transcriptomic, methylation and proteomic screening approaches. The majority of Barrett's oesophagus patients remain undiagnosed in the general population. In order to develop a tool to screen for Barrett's oesophagus in the primary care setting, minimally invasive sampling methods coupled with immunocytology-based biomarkers are currently being assessed. Biomarkers may also have utility in surveillance programmes by allowing endoscopic interval to be adjusted according to individual neoplastic risk. Many individual biomarkers have been proposed in this regard, but have frequently been assessed in studies of limited power, or have lacked sufficient sensitivity or specificity when assessed in wider population-based studies. Biomarker panels may provide a route forward. In this regard, a panel of methylation markers has shown promise in a multicentre, double-blind, validation study. Biomarkers are also being developed to improve detection of high-grade dysplasia and oesophageal adenocarcinoma, utilizing brush cytology combined with FISH (fluorescence in situ hybridization), and to assess therapeutic success and risk of complication during photodynamic therapy. Finally, we outline progress in identifying alternative sources of biomarkers for this condition.

scholarly journals Dietary inflammatory index and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case–control study

2017 ◽  
Vol 117 (9) ◽  
pp. 1323-1331 ◽  
Author(s):  
Nitin Shivappa ◽  
James R. Hebert ◽  
Lesley A. Anderson ◽  
Martha J. Shrubsole ◽  
Liam J. Murray ◽  
...  
Keyword(s):  
Reflux Oesophagitis ◽  
Cell Cancer ◽  
Acid Reflux ◽  
Population Based ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Dietary Inflammatory Index ◽  
Barrett's Oesophagus ◽  
Inflammatory Index ◽  
Reflux Œsophagitis

AbstractThe dietary inflammatory index (DIITM) is a novel composite score based on a range of nutrients and foods known to be associated with inflammation. DII scores have been linked to the risk of a number of cancers, including oesophageal squamous cell cancer and oesophageal adenocarcinoma (OAC). Given that OAC stems from acid reflux and that the oesophageal epithelium undergoes a metaplasia-dysplasia transition from the resulting inflammation, it is plausible that a high DII score (indicating a pro-inflammatory diet) may exacerbate risk of OAC and its precursor conditions. The aim of this analytical study was to explore the association between energy-adjusted dietary inflammatory index (E-DIITM) in relation to risk of reflux oesophagitis, Barrett’s oesophagus and OAC. Between 2002 and 2005, reflux oesophagitis (n219), Barrett’s oesophagus (n220) and OAC (n224) patients, and population-based controls (n256), were recruited to the Factors influencing the Barrett’s Adenocarcinoma Relationship study in Northern Ireland and the Republic of Ireland. E-DII scores were derived from a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of oesophageal lesions according to E-DII intakes, adjusting for potential confounders. High E-DII scores were associated with borderline increase in odds of reflux oesophagitis (OR 1·87; 95 % CI 0·93, 3·73), and significantly increased odds of Barrett’s oesophagus (OR 2·05; 95 % CI 1·22, 3·47), and OAC (OR 2·29; 95 % CI 1·32, 3·96), when comparing the highest with the lowest tertiles of E-DII scores. In conclusion, a pro-inflammatory diet may exacerbate the risk of the inflammation-metaplasia-adenocarcinoma pathway in oesophageal carcinogenesis.

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study

Gut ◽  
2014 ◽  
Vol 64 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Shivaram K Bhat ◽  
Damian T McManus ◽  
Helen G Coleman ◽  
Brian T Johnston ◽  
Christopher R Cardwell ◽  
...  
Keyword(s):  
Population Based ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Population Based Study ◽  
Barrett's Oesophagus

scholarly journals The proportion of oesophageal adenocarcinoma patients with prior barrett's oesophagus: results from a large population based cohort

Gut ◽  
2011 ◽  
Vol 60 (Suppl 1) ◽  
pp. A169-A169
Author(s):  
S. Bhat ◽  
H. G. Coleman ◽  
D. McManus ◽  
A. T. Gavin ◽  
L. J. Murray ◽  
...  
Keyword(s):  
Large Population ◽  
Population Based ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus

scholarly journals P-OGC95 Understanding the molecular age of Barrett’s oesophagus in a population-representative sample of patients

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Talita Oliveira ◽  
McKenna Lewis ◽  
Laura Smyth ◽  
Richard Turkington ◽  
Amy Jayne McKnight ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Population Based ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Patient Specific ◽  
Biological Aging ◽  
Computational Tools ◽  
Barrett's Oesophagus ◽  
Genome Wide ◽  
Aging Rates

Abstract Background The incidence of oesophageal adenocarcinoma (OAC) increases dramatically with patient age but only a small proportion of patients with diagnosed Barrett’s oesophagus (BO), the precursor to OAC, will develop dysplasia and/or cancer. Beyond chronological age, biomarkers of progression that capture biological aging offer largely untapped potential for objectively identifying BO patients at highest risk of progression, who could undergo personalised surveillance at shorter intervals. We have developed computational tools to determine tissue-specific aging using genome-wide methylation data as a “molecular clock” for estimating patient-specific BO dwell times at the time of incident diagnosis that cannot be clinically measured by other means.  Methods Using the population-based Northern Ireland BO register in a retrospective study, we have identified 46 non-dysplastic BO patients who have 2-4 serial endoscopic biopsies each, and have not progressed to OAC (age range 29-77 years).  FFPE biopsies for 10 age-matched patients who had prevalent HGD/OAC at index BO diagnosis were also retrieved. DNA has been extracted, quantified using fluorescence, quality checked through qPCR, and prepared for Illumina EPIC methylation arrays. We created a Python package called “MethylDrift” to determine genome-wide aging rates in patient data. Model outputs are used in the molecular clock for BO tissue age. Results We used MethylDrift to quantify aging rates in both cross-sectional data (population-level epigenetic drift) and longitudinal data within the same patients to obtain individual aging rates. Computational analyses using our previously developed Bayesian framework for the BO molecular clock will be applied to estimate the molecular age of BO in patients, i.e., how long the patient has been living with BO since onset of metaplasia. Results will be compared between age groups, birth cohorts, sex, and importantly between dysplastic and non-dysplastic BO to evaluate biomarker potential. Data analysis is ongoing, and the final results will be presented at the meeting. Conclusions Our results from this nested case-control study demonstrate feasibility and generate pilot data on molecular age as a proxy of BO duration at the time of incident diagnosis, in a large population-based registry of patients with BO. This will inform our computational tools for determining biological aging and can be applied in future work to investigate progression risk according to molecular age. Ultimately, this biomarker could inform surveillance frequency for BO patients, enable earlier detection of neoplastic progression, leading to improved patient outcomes and optimal distribution of limited endoscopy capacity for surveillance.

scholarly journals Dietary magnesium, calcium:magnesium ratio and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case–control study

2015 ◽  
Vol 115 (2) ◽  
pp. 342-350 ◽  
Author(s):  
Qi Dai ◽  
Marie M. Cantwell ◽  
Liam J. Murray ◽  
Wei Zheng ◽  
Lesley A. Anderson ◽  
...  
Keyword(s):  
Reflux Oesophagitis ◽  
Survival Rates ◽  
Developed Countries ◽  
Population Based ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Dietary Intakes ◽  
Barrett's Oesophagus ◽  
Colonic Carcinogenesis ◽  
Reflux Œsophagitis

AbstractEvidence suggests a role of Mg and the ratio of Ca:Mg intakes in the prevention of colonic carcinogenesis. The association between these nutrients and oesophageal adenocarcinoma – a tumour with increasing incidence in developed countries and poor survival rates – has yet to be explored. The aim of this investigation was to explore the association between Mg intake and related nutrients and risk of oesophageal adenocarcinoma and its precursor conditions, Barrett’s oesophagus and reflux oesophagitis. This analysis included cases of oesophageal adenocarcinoma (n218), Barrett’s oesophagus (n212), reflux oesophagitis (n208) and population-based controls (n252) recruited between 2002 and 2005 throughout the island of Ireland. All the subjects completed a 101-item FFQ. Unconditional logistic regression analysis was applied to determine odds of disease according to dietary intakes of Mg, Ca and Ca:Mg ratio. After adjustment for potential confounders, individuals consuming the highest amounts of Mg from foods had significant reductions in the odds of reflux oesophagitis (OR 0·31; 95 % CI 0·11, 0·87) and Barrett’s oesophagus (OR 0·29; 95 % CI 0·12, 0·71) compared with individuals consuming the lowest amounts of Mg. The protective effect of Mg was more apparent in the context of a low Ca:Mg intake ratio. No significant associations were observed for Mg intake and oesophageal adenocarcinoma risk (OR 0·77; 95 % CI 0·30, 1·99 comparing the highest and the lowest tertiles of consumption). In conclusion, dietary Mg intakes were inversely associated with reflux oesophagitis and Barrett’s oesophagus risk in this Irish population.

scholarly journals Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323906
Author(s):  
Jue-Sheng Ong ◽  
Jiyuan An ◽  
Xikun Han ◽  
Matthew H Law ◽  
Priyanka Nandakumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Testing ◽  
Association Studies ◽  
Barrett’S Oesophagus ◽  
Oesophageal Reflux ◽  
Oesophageal Adenocarcinoma ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Disease Heterogeneity ◽  
Barrett's Oesophagus

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.

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