A Sibling Pair Study To Identify Barrett's Oesophagus Susceptibility Genes
- 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.
- 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
PROJECTED ACCRUAL: A total of 200 sibling pairs will be accrued for this study.
Familial incidence of heartburn and Barrett's esophagus in first and second degree relatives of patients with Barrett's esophagus
Rebecca Fitzgerald, MD
Hutchison Cancer Research Unit