scholarly journals Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma

Gut ◽  
2016 ◽  
Vol 66 (10) ◽  
pp. 1739-1747 ◽  
Author(s):  
Matthew F Buas ◽  
Qianchuan He ◽  
Lisa G Johnson ◽  
Lynn Onstad ◽  
David M Levine ◽  
...  
Keyword(s):  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus ◽  
Germline Variation

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.

scholarly journals MIC-1/GDF15 in Barrett’s oesophagus and oesophageal adenocarcinoma

2015 ◽  
Vol 112 (8) ◽  
pp. 1384-1391 ◽  
Author(s):  
O M Fisher ◽  
A J Levert-Mignon ◽  
S J Lord ◽  
K K M Lee-Ng ◽  
N K Botelho ◽  
...  
Keyword(s):  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus

scholarly journals Practical early cancer detection: distinguishing stable from unstable genomes in pre-cancerous tissues

2020 ◽  
Author(s):  
Sarah Killcoyne ◽  
Rebecca C. Fitzgerald
Keyword(s):  
Cancer Detection ◽  
Early Cancer ◽  
Gene Mutations ◽  
Malignant Progression ◽  
Early Cancer Detection ◽  
Barrett’S Oesophagus ◽  
Oesophageal Adenocarcinoma ◽  
Barrett's Oesophagus ◽  
Individual Gene ◽  
Future Risk

Summary Barrett’s oesophagus has been known for many years to display early changes to the genome consistent with the risk for oesophageal adenocarcinoma. Recently we have shown that this information can be used without knowledge of individual gene mutations to accurately predict a patient’s future risk of malignant progression.

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.

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