Predisposing genetic risk factors for Barrett*s Esophagus

Barrett*s esophagus (BE) is the second most common premalignant lesion in the
Western world after large bowel polyps. BE affects over 2% of the adult
population and, unlike bowel polyps, lacks any proven effective therapy.
In the majority of cases, BE is associated with chronic gastro-esophageal
reflux disease (GERD), including esophagitis. In addition, there are structural
changes, mainly hiatus hernia, in the lower esophagus in over 80% of BE
patients. This allows both acid and bile to remain immediately adjacent to the
esophageal epithelium. The annual risk of esophageal adenocarcinoma (EAC) in BE
is approximately 0.5-1% per year. The incidence of EAC has been rising by 3%
each year for the last 30 years and is now the fifth commonest cancer in the
UK. Despite modern multimodality therapy, the prognosis of EAC remains poor,
with a 9-15% 5-year survival.
The etiology of BE is not well characterised. Environmental factors, such as
obesity are associated with GERD, BE and EAC. There is also evidence of causal
genetic factors; the relative risks are increased 2-4 fold for GERD, BE and EAC
when one first-degree relative is affected. However, extensive candidate gene
searches have so far failed to identify genetic variants that are associated
with BE risk.
Using cohorts from UK and Dutch populations (in collaboration with Prof.
Jankowski) we want to identify variants associated with BE in this genome-wide
association study.

Primary Objective: To identify variants in the humane genome that are
associated with BE risk.
Secondary Objective(s): We will collect information on BE length, complication
of BE (dysplasia, ulcer, stricture or EAC), presence of esophagitis and hiatal
hernia from medical records. Further, information on patients* BMI, medication
and cardiac history will be collected.

This will be a genome-wide association study on BE cases and controls. Patients
with known BE will be collected from the cohort of BE patients in the Tergooi
ziekenhuizen and Kennemer Gasthuis.
Patients will be contacted with a letter, including patient information folder
and an informed consent form. Patients not reacting within 14 days will receive
a reminder letter.
Patients who are willing to participate in the study and have given written
informed consent will be asked for a single visit at their hospital (Tergooi
ziekenhuizen, Kennemer Gasthuis) for a single withdrawal of 5ml of EDTA blood.
No further visits to the hospital will be necessary.

The risks of drawing blood from a vein include discomfort at the site of
puncture; possible bruising and swelling around the puncture site; rarely an
infection; and, uncommonly, faintness from the procedure.