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3 New Genetic Mutations Establish Hereditary Link in Esophageal Cancer

Ben Leach
Published: Wednesday, Jul 27, 2011

Section of the human esophagus.

Section of the human esophagus.

Three new genetic mutations have been identified in patients with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). The mutations suggest a previously unknown heritable cause for these esophageal diseases.

A case-control mutation analysis was performed on 255 participants, of which 116 were patients who had been diagnosed with BE, EAC, or both. The analysis was performed as part of a larger BE/EAC study conducted at 16 sites across the United States from 2005 through 2010. Single-SNP, haplotype, and integrative genomic validation identified potentially mutated genes in 116 patients with BE/EAC. Further screening revealed germline mutations of the genes MSR1, ASCC1, and CTHRC1 in 13 (11.2%) patients (all P < .001).

Mutations in the gene MSR1 were the most common of the 3 variations, appearing in 8 of the 116 patients (7%; 95% confidence interval, 0.030-0.130, P < .001). Furthermore, these 3 genetic mutations were not found in the 139 patients in the control group who were not affected by BE or EAC. Proper identification of the MSR1 and CTHRC1 mutations was replicated in an independent validation series.

The study results will be published in the July 27, 2011 edition of the Journal of the American Medical Association.

Considered a precursor of EAC, BE occurs in 1% to 10% of the general population, oftentimes in people who already have gastroesophageal reflux disease (GERD), a condition that could affect as much as 35% of Americans. The incidence of EAC in Europe and the United States has increased 350% in the last 30 years, resulting in 14,500 deaths and 16,640 new cases diagnosed in the United States in 2010.

Charis Eng, MD, PhD, chair and founding director of the Genomic Medicine Institute of Lerner Research Institute at Cleveland Clinic, said the study provides valuable insight into the genetic origins of BE/EAC. As genetic markers are identified for these 3 genes, improved risk assessment, early detection, and disease management techniques could be developed, all of which may lead to higher survival rates among patients. MSR1 is associated with inflammation and apoptosis and has also been linked to prostate cancer, while ASCC1 and CTHRC1 have been linked to oncologic and inflammatory pathways.

“We are absolutely thrilled to now know three distinct genes that link to BE/EAC,” Eng said in a press release. “This is essential for improving risk assessment, disease management, and saving lives.”


Orloff M, Peterson C, He X, et al. Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA. 2011;306(4):410-419. doi:10.1001/jama.2011.1029.



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