Researchers identify genetic mutations associated with diseases of the esophagus

ScienceDaily (July 26, 2011) — Mutations in three genes have been identified that are more prevalent in patients with esophageal cancer and Barrett esophagus, a premalignant metaplasia (change in cells or tissue) caused by chronic gastroesophageal reflux disease (GERD), according to preliminary research reported in the July 27 issue of JAMA.See Also:Health & MedicineGenesBrain TumorParkinson's ResearchDiseases and ConditionsGastrointestinal ProblemsPersonalized MedicineReferenceTumor suppressor geneBRCA1BRCA2Tumor

The incidence of esophageal adenocarcinoma (EAC) in the United States and Europe has increased 350 percent since 1970, with the cause uncertain. Esophageal adenocarcinoma is believed to be preceded by Barrett esophagus (BE), according to background information in the article. Barrett esophagus is common, estimated to occur in 1 percent to 10 percent of the general population. "Finding predisposition genes may improve premorbid risk assessment, genetic counseling, and management," the authors write.

Charis Eng, M.D., Ph.D., of the Cleveland Clinic, and colleagues conducted a study to identify a gene or genes associated with BE/EAC predisposition. The research included an analyses of 21 concordant (both)-affected sibling pairs with BE/EAC and 11 discordant sibling pairs (2005-2006). The study also included data from 176 white patients with BE/EAC and 200 ancestry-matched controls (2007-2010). Data from 19 BE/EAC tissues yielded 12 "priority" candidate genes for mutation analysis. Genes that showed mutations in cases but not in controls were further screened in 58 cases.

Analyses indicated that three major genes, MSR1, ASCC1, and CTHRC1 were associated with BE/EAC. Mutational analyses of the 12 priority candidate genes in BE/EAC cases found mutations in these three genes in 13 of 116 patients (11.2 percent), with the most frequently mutated being MSR1 (approximately 7 percent), followed by ASCCl and CTHRC1. "Findings of germline