Genetic Biomarkers of Barrett’s Esophagus Susceptibility and Progression to Dysplasia and Cancer: A Systematic Review and Meta-Analysis

Abstract

Barrett’s esophagus (BE) is a common and important precursor lesion of esophageal adenocarcinoma (EAC). A third of patients with BE are asymptomatic, and our ability to predict the risk of progression of metaplasia to dysplasia and EAC (and therefore guide management) is limited. There is an urgent need for clinically useful biomarkers of susceptibility to both BE and risk of subsequent progression. This study aims to systematically identify, review, and meta-analyze genetic biomarkers reported to predict both. A systematic review of the PubMed and EMBASE databases was performed in May 2014. Study and evidence quality were appraised using the revised American Society of Clinical Oncology guidelines, and modified Recommendations for Tumor Marker Scores. Meta-analysis was performed for all markers assessed by more than one study. A total of 251 full-text articles were reviewed; 52 were included. A total of 33 germline markers of susceptibility were identified (level of evidence II–III); 17 were included. Five somatic markers of progression were identified; meta-analysis demonstrated significant associations for chromosomal instability (level of evidence II). One somatic marker of progression/relapse following photodynamic therapy was identified. However, a number of failings of methodology and reporting were identified. This is the first systematic review and meta-analysis to evaluate genetic biomarkers of BE susceptibility and risk of progression. While a number of limitations of study quality temper the utility of those markers identified, some—in particular, those identified by genome-wide association studies, and chromosomal instability for progression—appear plausible, although robust validation is required.Electronic supplementary materialThe online version of this article (doi:10.1007/s10620-015-3884-5) contains supplementary material, which is available to authorized users.

Kosten-Effektivitäts- und Kosten-Nutzwert-Analysen der Antirefluxmedizin

“…Risikoberechnungen für die hochgradige Dysplasie sind nur geringfügig höher [12]. Wenngleich bisher viele molekulargenetische Biomarker für den Barrett-Ösophagus sowie für die Progression von der Dysplasie zum Karzinom identifiziert wurden [13], sind die derzeitigen klinischen Anwendungsmöglichkeiten zur spezifischen, individuellen Risikoprädiktion limitiert. Zu berücksichtigen ist hierbei, dass ca.…”

“…Zu berücksichtigen ist hierbei, dass ca. 1/3 der Patienten mit Barrett-Ösophagus asymptomatisch sind [13] und mindestens 40 % der Patienten mit Barrett-Karzinom keine klinischen Hinweise auf eine gastroösophageale Refluxkrankheit aufweisen [14], was möglicherweise darauf zurückzuführen ist, dass die subjektive Perzeption des Symptoms "Reflux" bei entsprechender Zelltransformation zum Barrett abnimmt.…”

Research priority setting in Barrett's oesophagus and gastro-oesophageal reflux disease

“…P53 immunohistochemistry remains the only biomarker recommended for clinical use to aid histopathological diagnosis (22), but the efficacy of this biomarker has met with some doubt in a recent consensus statement (23). To date it has been very challenging to predict the progression of non-dysplastic BO using biomarkers, especially translating research advances into routine clinical use (24). The mutational profile of BO appears highly heterogenous with mutations already occurring in non-dysplastic tissue.…”

Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

“…The genesis of metaplasia is thought to be a response to chronic tissue inflammation [25] and is known as Barrett’s esophagus (BE) [26,27,28]. Although a number of papers has been published on this topic, there is still relatively little information available about tissue homeostasis in the epithelium of the esophagus.…”