Familial Barrett’s Esophagus: Clues to Genetic Risks for Esophageal Adenocarcinoma

Esophageal adenocarcinoma is a particularly deadly neoplasm, and the incidence of it has been rising at an alarming rate in recent decades in Western countries [1, 2]. Barrett’s esophagus has been recognized as a precursor lesion for cancer, and screening and subsequent surveillance or other intervention for this lesion is an attractive proposition. Despite the rising incidence, the cancer still remains relatively uncommon. Therefore, selecting highrisk patients for screening, surveillance, or intervention is important in order to make the practice economically reasonable. Risk factors have been established for the cancer and for Barrett’s esophagus, including male gender, white race, older age, symptoms of gastroesophageal reflux, obesity, tobacco use, and absence of infection with Helicobacter pylori. However, most of these factors are highly prevalent in Western societies, so more specific risk factors would improve the efficiency of clinical practice. The association with white race might be because of environmental differences among races, but also suggests that genetic factors play an important role. Obviously, humans are not evolving rapidly enough to explain the rising incidence of esophageal adenocarcinoma, which is certainly because of relatively recent changes in environment or behavior. However, those changes in environment and behavior may interact with genetic factors, such that only genetically predisposed individuals develop the cancer in the modern setting of obesity and low prevalence of Helicobacter pylori. Indeed, a family history of esophageal adenocarcinoma or Barrett’s esophagus has been associated with the presence of both of those diagnoses [3]. A number of case reports of individual families suggest an autosomal dominant pattern of inheritance with incomplete penetrance [4–6]. Familial effects on the risk of esophageal adenocarcinoma may act via the promotion of other known risk factors (such as obesity or gastroesophageal reflux), via the promotion of Barrett’s esophagus among those with the recognized risk factors, via the promotion of neoplastic transformation within Barrett’s esophagus, or combinations of these loci of effects. In this issue of Digestive Diseases and Sciences, Ash and colleagues have begun to address these effects by studying their cohort of patients with Barrett’s esophagus [7]. Records of nearly 1,000 patients with Barrett’s esophagus were abstracted regarding their family history of either Barrett’s esophagus or esophageal cancer, and those with a positive history were interviewed for details. Nearly 6% of patients with Barrett’s esophagus were found to have a positive family history. The investigators then compared these familial cases of Barrett’s esophagus with the non-familial cases, seeking differences in demographics or clinical characteristics. Of note, they found no difference in gender, race, smoking history, presence of Helicobacter pylori, hiatal hernia, or length of Barrett’s esophagus. The investigators did find that familial cases were younger, and less likely to harbor neoplasia; however, they attribute these differences to referral bias, because patients with neoplasia are frequently referred to their center from outside practices, and patients with familial Barrett’s esophagus without neoplasia may be more likely to be referred to them than other non-neoplastic Barrett’s esophagus patients. The younger age of the familial Barrett’s J. H. Rubenstein (&) Veterans Affairs Center for Clinical Management Research, VA Medical Centre, 111-D, 2215 Fuller Road, Ann Arbor, MI 48105, USA e-mail: jhr@med.umich.edu