The Genetics of Barrett’s Esophagus: A Familial and Population-Based Perspective

Abstract

Barrett's esophagus (BE) is intestinal metaplasia of the lower esophagus and a precursor lesion for esophageal adenocarcinoma (EAC). Both are important health issues as they have rising incidences in the Western world. Improving the management of BE relies on understanding the underlying biology of this disease, but the exact biological mechanisms have been difficult to determine. BE is generally thought to be an acquired condition that develops secondarily to chronic gastroesophageal reflux. However, multiple reports of familial clustering of patients with BE and/or EAC suggest a possible inherited predisposition to BE may be driving this condition, at least in a subset of patients. Identifying the genetic variants that predispose to BE in these families would open up the possibility for blood-based screening tests that could inform decision-making in regard to surveillance strategies, particularly for relatives of patients with BE and/or EAC. Perhaps more importantly, understanding the genetic mechanisms that predispose to BE may provide valuable insights into the biology of this condition and potentially identify novel targets for therapeutic intervention. Here we review the current evidence for a genetic predisposition to BE and discuss the potential implications of these findings.

The Epidemiology of Esophageal Adenocarcinoma

“…Approximately 7% of cases of Barrett's esophagus (BE) or EAC occur within families. [24][25][26] Familial cases develop at an earlier age than sporadic EACs. 27,28 Other risk factors for EAC, such as regurgitation, smoking and obesity, are less prevalent among individuals with familial BE or EAC.…”

“…43,44 Genetic factors associated with EAC and clinical utility Up to one third of EAC may be hereditary and attributed to a combination of germline mutations, 45 although single mutations are associated with only a 20% increase in risk of EAC, at most. 26 However, the sharp increase in EAC incidence in many countries cannot be accounted for by changes in the population's genetic make-up over a timeframe of only 50 years. Genetic predisposition might account for some of the variation in geographical incidence of EAC.…”

“…The clinical utility of understanding genetic variants associated with EAC risk is perhaps limited, given the common prevalence and relatively low risk of EAC associated with many of the SNP 26,47 However, the contribution of genetic studies to the enhanced biological understanding of susceptibility to EAC should not be underestimated. It is important to study interactions between genetic and environmental factors that affect risk for EAC, as these might increase our understanding of temporal trends in EAC incidence.…”

Establishment of an international database for genetic variants in esophageal cancer

“…In addition, a genetic component has been shown to be important. Several studies have indicated genetic variations in esophageal cancer . There is evident genetic predisposition to the disease due to inherited variants and the effects of acquired somatic variants.…”

“…Several studies have indicated genetic variations in esophageal cancer. [1][2][3][4][5] There is evident genetic predisposition to the disease due to inherited variants and the effects of acquired somatic variants. To be able to understand the disease progress and genetic relevance, it is essential to collect, organize, distribute, analyze, and interpret genetic variations in esophageal cancer.…”