• Familial incidence of heartburn and Barrett's esophagus in first and second degree relatives of patients with Barrett's esophagus [ Designated as safety issue: No ]
  
• Susceptibility genes for Barrett's esophagus in affected sibling pairs [ Designated as safety issue: No ]
  
• Gene-environment interactions, such as smoking, alcohol, and Helicobacter pylori status, on familial susceptibility to heartburn and Barrett's esophagus [ Designated as safety issue: No ]
  

• Comparison of the mortality from esophageal adenocarcinoma in family members with heartburn and Barrett's esophagus with deaths from other causes [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To investigate the familial incidence of heartburn and Barrett's esophagus in first and second degree relatives of patients with Barrett's esophagus in the United Kingdom.
• To determine susceptibility genes for Barrett's esophagus in affected sibling pairs.
• To examine gene-environment interactions, such as smoking, alcohol, and Helicobacter pylori status, on familial susceptibility to heartburn and Barrett's esophagus.

Secondary

• To compare the mortality from esophageal adenocarcinoma in family members with heartburn and Barrett's esophagus with deaths from other causes.

OUTLINE: This is a multicenter study.

Patients complete a family history questionnaire. Epidemiological data is also collected about environmental exposures, such as smoking and alcohol history. Any siblings or other living family members affected by heartburn identified from this survey are then contacted to validate their symptoms/diagnoses and to collect other relevant epidemiological data. Family members with heartburn are offered a screening endoscopy for the presence of Barrett's esophagus. In the absence of an endoscopy, a symptom nomogram predictive for the presence of Barrett's esophagus is used.

Patients and their siblings, as well as any other willing family member (affected or non-affected) are asked to have a blood sample (EDTA tube for genetic analysis and a serum sample for Helicobacter pylori status) taken by their physician. Genomic DNA is extracted from lymphocytes and a genome-wide scan is performed using a standard marker set. A computer program is used to verify sibling relationships. Individuals not found to be full siblings are excluded from subsequent analyses. Maximum likelihood score (MLS) and the nonparametric linkage score (NPL) is used to estimate the degree of linkage.

All study participants are flagged with the National Health Service (NHS) Central Register to ascertain the future mortality from esophageal adenocarcinoma compared with deaths from other causes.

PROJECTED ACCRUAL: A total of 200 sibling pairs will be accrued for this study.