Together, the high prevalence of BE and the low cancer incidence among unselected BE cases, versus the burden of treatment and low survival of EAC ask for smart strategies to select BE patients who are most likely to benefit from surveillance and intervention. the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and malignancy are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and JT010 intervention techniques in coming years. and presence of Barretts esophagus . These factors interplay with genetic predisposition. Barretts esophagus shows a certain degree of familial clustering. In a Dutch survey of 603 patients, definite familial VEGF-D clustering was found in 7% of patients . This JT010 was likely an underestimate of the true prevalence of familial clustering, since a further 44% of participants reported that familial co-occurrence was either unknown or likely. Recent large populace caseCcontrol studies recognized more than 20 genetic variants predisposing for Barretts esophagus in populations of European ancestry [7, 8]. Risk Prediction Together, this knowledge led to a range of tools to predict the presence of Barretts esophagus in specific populations. Most of these were based on demographic and clinical data alone. These models tend to have fair overall performance in predicting the likelihood that a subject will have Barretts esophagus. A recent study aimed to combine these with familial JT010 history . Based on close to 900 Barretts cases, the authors developed a model using eight risk factors including age, sex, smoking, heartburn frequency, and use of acid suppressants. They combined this with family history. For 50-year-old subjects, the model predicted Barretts esophagus prevalences ranging between 3 and 33% in men, and 0.5 and 10% in women . A recent study went further and aimed to predict the risk of Barretts esophagus and esophageal adenocarcinoma based on demographic and way of life data in combination with an individuals genetic profile . The authors analyzed 3288 Barretts cases, 2511 patients with esophageal adenocarcinoma, and 2177 controls from different cohorts. Subjects were assessed for GERD symptoms as well as age, sex, smoking habits, body mass index, and use of NSAIDs. Much like previous models, these factors were moderately accurate to discriminate between Barretts cases and controls with an area under the curve ranging between approximately 0.64 and 0.67 for demographics plus way of life factors alone and GERD history alone, and 0.79 when combining both. Each individual was further assigned a polygenic risk score based on their quantity of risk alleles (0, 1, or 2) for each of 23 genetic variants identified as being associated with Barretts esophagus. For each variant, the allele number was weighted in relation to the effect estimate of the genetic variant. The sum of these weighted allele counts was then divided by 23 to yield one polygenic risk score . Adding the polygenic risk score to the other factors only marginally increased prediction accuracy with an AUC of 0.799 for all those factors combined. The authors rightfully concluded that the small contribution of genetic data to their prediction tool does not justify their clinical use. Progression of Barretts Esophagus These data are all relevant for an adequate understanding of the natural history of Barretts esophagus. They provide insight into the occurrence of Barretts metaplasia in men and women, and a background to determine progression rates to dysplasia and malignancy. These two then appear closely linked, as we will discuss. Similar to the development of knowledge around the epidemiology of Barretts esophagus, the first knowledge on progression rates to dysplasia and malignancy also came from endoscopy series, in particular from tertiary care centers. One of the oldest cohorts in this respect was the Rotterdam cohort. It consisted of a cohort of 166 patients diagnosed between 1973 and 1986, and followed since then. They first did not receive endoscopic surveillance; this started in 2001. The most recent analysis of this cohort included 130 patients with an average age at initial diagnosis of 62.4?years (range 14.4C92.3?years) and an average follow-up of 14.7?years (range 2.1C32.0) . Thirteen.