Germline Mutations Tied to Barrett Esophagus

Wednesday, July 27, 2011 (Last Updated: 07/28/2011)

WEDNESDAY, July 27 (HealthDay News) -- Three gene mutations, MSR1, ASCC1, and CTHRC1, are significantly associated with Barrett esophagus (BE) and/or esophageal adenocarcinoma (EAC), of which the MSR1 mutation is the most frequent but is only present in a small percentage of cases, according to a study published in the July 27 issue of the Journal of the American Medical Association.

Mohammed Orloff, Ph.D., from the Genomic Medicine Institute in Cleveland, and colleagues aimed to identify risk alleles or mutated genes associated with BE/EAC. A total of 21 concordant and 11 discordant sibling pairs with BE/EAC were analyzed between 2005 and 2006. Significant germline genomic regions were validated and fine mapped in an independent series of 176 white patients with BE/EAC and 200 ancestry-matched controls between 2007 and 2010. A total of 12 priority candidate genes were identified by integrating data from significant genomic regions and 19 BE/EAC tissues with publicly available somatic gene expression. Mutation analysis was carried out in 116 individuals with BE/EAC, 139 controls with MSR1, and 125 controls with ASCC1. Genes that showed mutations in cases but not in controls were screened in an independent validation series of 58 BE/EAC cases.

The investigators identified three major genes that were significantly associated with BE/EAC -- MSR1, ASCC1, and CTHRC1 -- with germline mutations in 11.2 percent of cases. The MSR1 gene was mutated most frequently, with c.877C>T (p.R293X) in eight of 116 cases (proportion, 0.069). The validation series confirmed germline MSR1 mutations in two of the 58 cases.

"MSR1 was significantly associated with the presence of BE/EAC in derivation and validation samples, although it was only present in a small percentage of the cases," the authors write.

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Specialties Dermatology
Hematology & Oncology

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