Researchers identify genetic mutations associated with diseases of the esophagus

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.

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 [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.
(JAMA. 2011;306[4]410-419. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Media Advisory: To contact corresponding author Charis Eng, M.D., Ph.D., call Dan Doron at 216-312-0428 or email

The JAMA Network Journals

Related Esophageal Cancer Articles from Brightsurf:

Pathological regression of lymph nodes better predicts esophageal cancer survival
A team of researchers led by Osaka University established a new pathological grading system to evaluate the therapeutic effect of neoadjuvant chemotherapy (NAC) for metastatic lymph nodes (LNs) removed in esophageal cancer (EC) surgery, demonstrating that the system predicts recurrence and prognosis in EC patients better than conventional systems.

Racial disparities in surgery rates for esophageal cancer
Black patients with esophageal cancer are less likely to receive life-saving surgery for early-stage disease than white patients.

Portable 'electronic nose' can accurately pick up esophageal cancer precursor
A portable 'electronic nose' can accurately pick up the precursor condition to food pipe (esophageal) cancer, known as Barrett's esophagus, indicates a proof of principle study, published online in the journal Gut.

A new machine learning approach detects esophageal cancer better than current methods
Dartmouth scientists have proposed a new machine learning model for identification of esophageal cancer that could open new avenues for applying deep learning to digital pathology.

Lymph nodes can predict survival in patients with esophageal cancer
It is difficult for physicians to estimate recurrence and survival in patients with esophageal cancer.

New model improves staging and risk predictions for esophageal cancer patients
A new nomogram for assessing metastatic risk in esophageal cancer patients shows promise for more accurate risk-stratification, which is particularly relevant for stage T2 patients.

Combo of virotherapy and radiotherapy shows early promise in patients with esophageal cancer
The experimental oncolytic adenovirus telomelysin (OBP-301) in combination with radiotherapy was safe and showed early clinical efficacy in vulnerable patients with esophageal cancer, according to results from a phase I clinical trial presented at the AACR Annual Meeting 2019, March 29-April 3.

Drinking hot tea linked with elevated risk of esophageal cancer
Previous studies have revealed a link between hot tea drinking and risk of esophageal cancer, but until now, no study has examined this association using prospectively and objectively measured tea drinking temperature.

Test for esophageal cancer could save millions of lives
Cancer of the esophagus claims more than 400,000 lives around the world each year.

Genome offers clues to esophageal cancer disparity
A change in the genome of Caucasians could explain much-higher rates of the most common type of esophageal cancer in this population, a new study finds.

Read More: Esophageal Cancer News and Esophageal Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to