Oesophageal disease in systemic sclerosis: does heritability play a role?

OBJECTIVES: In systemic sclerosis (SSc) the most common gastrointestinal tract (GIT) complaint is gastroesophageal reflux disease (GERD), which may contribute to oesophagitis, stricture, Barrett's oesophagus, and oesophageal adenocarcinoma. We used a genealogical resource the Utah Population Database (UPDB) to analyse SSc pedigrees for hereditability of oesophageal disease.

METHODS: SSc, GERD, oesophagitis, stricture, Barrett's, and oesophageal adenocarcinoma were defined by ICD Ninth and Tenth Revision codes. Familial aggregation, relative risk (RR) of the GIT disease in SSc proband and their relatives was estimated by Cox regression model. The model (adjusted for sex and birth year) was used to evaluate the effects of having or being related to, a case or control for SSc, on GIT diseases.

RESULTS: We identified 2,227 unique SSc patients and 11,136 randomly selected controls matched by birth year, gender, and whether born in Utah, in an approximately 1:5 ratio. A SSc proband had a significant high risk of GERD (RR: 3.28), dysphagia (RR 5.58), oesophageal stricture (RR: 5.16), oesophagitis (RR: 4.86), and Barrett's (RR: 4.52) all with significant p-values <2e-16. First-degree relatives of a SSc proband were at elevated risk of GERD (RR: 1.14, p=6.85e-05), dysphagia (RR: 1.22 p=0.002), and oesophagitis (RR: 1.37, p=2.10e-06). First cousins (RR: 1.09, p=0.03) and spouses (RR; 1.37, p=0.02) were at increased risk of esophagitis and dysphagia.

CONCLUSIONS: These data suggest that independent of GERD, oesophagitis in SSc patients and their relatives may have both a hereditable and environmental etiology. There does not seem to be a heritable component to Barrett's oesophagus.