New Genetic Score Might Help Predict Risk of Barrett's Esophagus

By Will Boggs MD

April 22, 2019

NEW YORK (Reuters Health) - A new genetic risk score (GRS) might help predict the risk of Barrett's esophagus independently of most other risk factors, but the results are not conclusive, according to new research.

"We were able to provide further support for a genetic predisposition for this pre-cancerous condition that may operate independently of the typical risk factors one considers for Barrett's esophagus," Dr. Brian C. Jacobson from Boston University Medical Center told Reuters Health by email.

Several genetic variants appear to confer an increased risk for both Barrett's esophagus and esophageal adenocarcinoma, as do a number of common, modifiable factors, including BMI, smoking, alcohol consumption and heartburn duration.

Dr. Jacobson and colleagues used data from 401 incident Barrett's esophagus cases and 436 age-matched controls from the Nurses' Health Study I and II and the Health Professionals Follow-up Study to examine the effects and the potential effect modification between proposed Barrett's esophagus genetic loci and established environmental risk factors.

Current smoking, alcohol consumption and heartburn duration all showed positive associations with the risk of Barrett's esophagus.

Of the 46 single nucleotide polymorphisms (SNPs) investigated, none was significantly associated with Barrett's esophagus risk after correction for multiple testing.

A total of three of these SNPs were included in the main GRS (GRSb), but an additional GRS (GRSc) included all 46 SNPs.

In the unweighted GRSb (i.e., each SNP given equal weight), each one-allele increase was associated with a 20% increase in the risk of Barrett's esophagus, although there was only borderline significance (P=0.057).

Using a GRSb with the three SNPs weighted according to their beta coefficients in earlier studies, each increased unit of the score was associated with 3.13-fold increased risk of Barrett's esophagus, but again the result fell just short of statistical significance.

There was no association between the GRSc and the risk of Barrett's esophagus, the researchers report in the American Journal of Gastroenterology, April 4.

Smoking, alcohol consumption and heartburn duration did not interact with the individual SNPs, but there was a significant multiplicative interaction between smoking and the weighted GRSb.

"These pilot results suggest that larger studies in this area are warranted," the researchers conclude.

"In general, any time a genetic predisposition is found for a chronic condition, it provides us with new opportunities for understanding the pathophysiology behind that condition," Dr. Jacobson said. "In other words, we get one step closer to learning why the body changes in a way that makes it more susceptible to cancer. This, in turn, opens up opportunities to either prevent the condition in the first place, or to perhaps slow or stop its progression to cancer."

SOURCE: http://bit.ly/2Xopv00

Am J Gastroenterol 2019.

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