Hereditary Factors in Esophageal Adenocarcinoma

Background: The vast majority of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of EAC. Here, we review data from the published literature in order to address the current knowledge on familial EAC.

Summary: Although familial EAC comprises a relatively small group of patients, it is a clinically relevant category due to the poor prognosis of this type of cancer. Efforts should be made to identify specific genetic risk factors for familial EAC to enable identification of relatives at risk, since endoscopic surveillance can diagnose preneoplastic or early neoplastic lesions leading to early treatment, with improved outcome.

Key message: Although familial EAC comprises a relatively small group of patients, this is a clinically relevant category due to the poor prognosis. Efforts should be made to identify specific genetic risk factors for familial EAC in order to facilitate the identification of other family members with a predisposition for this type of cancer.

Practical implications: Approximately 7% of BE and EAC cases are considered familial. Age at diagnosis is generally lower for patients with familial EAC as compared to sporadic cases, while other known risk factors for EAC, such as male gender and Caucasian ethnicity, do not differ between the two groups. In several described families with clustering of EAC the pattern of inheritance seems to be consistent with a rare autosomal dominant genetic trait. However, some association has been found with (attenuated) familial adenomatous polyposis, mismatch repair deficiency and recently with the genes MSR1, ASCC1 and CTHRC1. Nevertheless, no specific genetic predisposition has yet been identified.