July 26, 2011
Researchers Identify Genetic Mutations Associated With Diseases Of The Esophagus
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.
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.
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 [those cells of an individual that have genetic material that could be passed to offspring] MSRl and CTHRCl mutations were replicated in an independent validation series," the authors write.
"These 3 genes together accounted for 11 percent of our cases, reflecting what is normally considered a moderate-to high-penetrance genetic load for a disease," they write. "Nonetheless, future independent studies are needed to replicate our data in other patient populations to confirm the conclusions."
The researchers add that larger cohort studies may be necessary to determine the usefulness of these genes and their variants in risk assessment and premorbid diagnosis.
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