Abstract and Introduction
Abstract
Background: Current guidelines recommend different screening approaches for individuals with a family history of Barrett’s oesophagus (BO) or oesophageal adenocarcinoma (OAC), varying from no screening to screening all individuals with a positive family history.
Aims: To determine evidence-based risk estimates for individuals with a family history of BO or OAC
Methods: We systematically searched Pubmed, Embase and Cochrane Library until October 2020 to identify all studies that reported on the association between family history and the risk of BO and OAC. Pooled summary estimates of adjusted relative risks and prevalence of familial BO/OAC with 95% confidence intervals (CIs) were calculated using a random effects model.
Results: Fourteen studies comprising 16 189 BO/OAC patients were analysed. Familial clustering was seen in 8.84% (95% CI: 5.54–13.82) and 4.37% (95% CI: 2.15–8.69) of patients with BO and OAC, respectively (nine studies). Screening first-degree relatives of BO patients had a diagnostic yield between 12% and 44% for BO (four studies). However, the yield for high-grade dysplasia and OAC was low (<2%). Individuals with a positive family history had a higher risk of having BO (aRR 3.26; 95% CI 1.43–7.40; I 2 = 46%; three studies) and OAC (aRR 2.19; 95% CI 1.14–4.21; I 2 = 48%; five studies) compared to individuals without a family history.
Conclusions: A verified family history of BO or OAC is a strong risk factor for both BO and OAC. A positive family history could be a clinically meaningful way to identify high-risk individuals who may benefit from early detection strategies.
Introduction
During the past 30 years, the incidence of oesophageal adenocarcinoma (OAC) has increased up to sixfold in Western countries.[1,2] With 35 000 new cases in 2018, nearly 50% of the worldwide cases of OAC occur in Europe and North America.[3] OAC still has a poor prognosis with a 5-year survival rate of only 20%, despite improvements in multimodality therapy.[4] The vast majority of patients with OAC present with locally advanced or metastatic disease, as symptoms of early OAC and its precursor lesions are often absent or barely distinct from gastro-oesophageal reflux disease (GERD).[1]
Barrett’s oesophagus (BO) is the major precursor of OAC, increasing the risk of developing OAC by a factor 10–30.[5,6] The population prevalence of BO is estimated to be approximately 1%-2%, which increases to 8%-20% in individuals with long-term GERD.[7,8] Unfortunately, in daily practice, >90% of patients with OAC never had prior endoscopy and only a minority of BO patients are currently diagnosed and under surveillance.[9] Hence, identifying patients with BO and early detection of OAC could be potentially helpful in reducing OAC-related mortality.
As the annual risk of OAC in patients with BO is low (0.1%-0.5%), the merits of population-based endoscopic screening are controversial.[5,10] It is therefore important to identify individuals at increased risk for BO and OAC. Already known risk factors for BO and OAC, including increasing age, male gender, Caucasian race, smoking, obesity and GERD, are in this regard helpful.[6]
Although the vast majority of BO and OAC cases are sporadic and caused by somatic mutations, several reports of families with multiple affected relatives suggest that there may be an underlying genetic susceptibility.[11–14] However, as the exact role of genetic factors in the development of BO and OAC has remained largely unclear, OAC is not included in familial risk management guidelines.[15] Clinical guidelines on the other hand suggest a role for endoscopic screening in individuals with a positive family history for BO or OAC.[16–19] Until now, recommendations for screening in these individuals are merely based on expert opinions and on small number of studies, and consequently recommendations vary between guidelines.[16–20]
Precise and valid evidence-based risk estimates for individuals with a family history of BO or OAC are needed to improve genetic counselling, provide rational advice, develop risk prediction models and to determine appropriate screening strategies. Understanding the association between family history and oesophageal metaplasia and related neoplasia may also improve the knowledge on the pathogenesis of BO and OAC and could be key to identify causal underlying germline mutations. The aim of this systematic review and meta-analysis was therefore to determine the prevalence of a positive family history in patients with BO and OAC. We furthermore aimed to assess the prevalence and the risk of BO and OAC in individuals with a positive family history.