High Genetic Propensity to Obesity Raises Risk of Esophageal Adenocarcinoma

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“People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with a low genetic propensity,” according to analyses of data from the Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study. “These analyses provide the strongest evidence to date that obesity is independently associated” with Barrett’s esophagus and esophageal adenocarcinoma and “is not due to confounding or bias inherent in conventional epidemiologic analyses,” Aaron P. Thrift, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues concluded in the Journal of the National Cancer Institute.

The analysis included data for 999 patients with esophageal adenocarcinoma, 2,061 patients with Barrett’s esophagus, and 2,169 population controls. Compared with control patients, patients with esophageal adenocarcinoma were older and more likely to be male, to have ever smoked, to have had symptoms of gastroesophageal reflux (the primary risk factor for esophageal adenocarcinoma and Barrett’s esophagus), and to have used acid-suppressant medications, whereas patients with Barrett’s esophagus were more likely to have ever had gastroesophageal reflux symptoms and to have used acid-suppressant medications.

“We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of body mass index on the risk of esophageal adenocarcinoma and Barrett’s esophagus,” the investigators stated. The Mendelian approach, they explained, “uses instrumental variables (eg, genetic variations that proxy for directly measured environmental factors) to make causal inferences about the relationship between a risk factor and an outcome; results from this method are considered to be analogous to the outcomes of a randomized trial.” For this trial, investigators used “a genetic risk score, derived from 29 genetic variants shown to be associated with body mass index, as an instrument for lifetime body mass index. A higher score indicates propensity to obesity.”

The genetic risk score was not found to be associated with potential confounders, including smoking and gastroesophageal reflux symptoms. In the instrumental variable analyses, esophageal adenocarcinoma risk increased by 16%, and Barrett’s esophagus risk increased by 12% per 1 kg/m2 increase in body mass index. “Body mass index was statistically significantly associated with esophageal adenocarcinoma and Barrett’s esophagus in conventional epidemiologic analyses,” the authors noted. ■

Thrift AP, et al: J Natl Cancer Inst 106(11):dju252, 2014.





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