Genetic factors shed light on Barrett's esophagus and adenocarcinoma

Reuters Health Information: Genetic factors shed light on Barrett's esophagus and adenocarcinoma

Genetic factors shed light on Barrett's esophagus and adenocarcinoma

Last Updated: 2016-09-01

By David Douglas

NEW YORK (Reuters Health) - Cystic fibrosis is among factors which may influence the complex relationship of genetics to Barrett's esophagus and adenocarcinoma, according to a large-scale meta-analysis.

As Dr. Puya Gharahkhani told Reuters Health by email, "Our findings provide targets for development of treatment and intervention strategies for clinical management of esophageal cancer in the future. In addition, combining our understanding of the genetic 'typos' which increase the risk of esophageal cancer with the previously known environmental risk factors will help to identify people who are at highest risk."

As reported August 12 online paper in The Lancet Oncology, Dr. Gharahkhani of the QIMR Berghofer Medical Research Institute, Brisbane, Australia, examined data pooled from four genome-wide association studies in Europe, North America, and Australia.

The studied involved 6167 patients with Barrett's esophagus, 4112 with adenocarcinoma, and more than 17,000 controls.

The researchers identified nine new risk loci associated with either condition or both. And, said Dr. Gharahkhani, the team "found a genetic marker which may help to identify patients who are at higher risk of transition from the precancerous changes of esophagus to the actual cancer."

The locus identified was near HTR3C and ABCC5 and was associated specifically with esophageal adenocarcinoma and was independent of Barrett's esophagus development.

The most strongly associated new risk variant, say the researchers, "is located within CFTR, mutations of which lead to cystic fibrosis. Patients with cystic fibrosis show highly increased incidence of gastro-esophageal reflux, and this reflux represents the main risk factor for Barrett's esophagus and esophageal adenocarcinoma."

The investigators concede, "Although we have provided bioinformatics evidence for the functional relevance of our findings, we do not provide in-vitro or in-vivo evidence for the biological function of these findings."

But, said Dr. Gharahkhani, "Our findings may have clinical implications in the future" and "ultimately, may result in reduced occurrence of new cases of this fatal cancer."

Commenting by email, Dr. Stephen Meltzer, author of an accompanying editorial, told Reuters Health, "The authors identified a possible link between hereditary Barrett's esophagus and the previously unrelated syndrome, cystic fibrosis. In addition, they found a genetic locus that increases the risk of esophageal cancer, independent of the risk of Barrett's esophagus."

Dr. Meltzer of The Johns Hopkins University School of Medicine, Baltimore, Maryland, added in his editorial that "if one or more of these variants prove to have a pathophysiological role in Barrett's esophagus or esophageal adenocarcinoma, they could become pivotal in the design of novel preventative or therapeutic strategies."


Lancet Oncol 2016.

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