Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a mendelian randomization study.

[esophageal adenocarcinoma]

Data from observational studies suggest that body mass index (BMI ) is causally related to esophageal adenocarcinoma (EAC ) and its precursor , Barrett 's esophagus (BE ). However , the relationships may be affected by bias and confounding .We used data from the Barrett 's and Esophageal Adenocarcinoma Genetic Susceptibility Study : 999 patients with EAC , 2061 patients with BE , and 2169 population controls . We applied the two -stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased , unconfounded effect of BMI on risk of EAC and BE . This was performed using a genetic risk score , derived from 29 genetic variants shown to be associated with BMI , as an instrument for lifetime BMI . A higher score indicates propensity to obesity . All tests were two -sided .The genetic risk score was not associated with potential confounders , including gastroesophageal reflux symptoms and smoking . In the instrumental variable analyses (IV ), EAC risk increased by 16 % (IV-odds ratio [OR ] = 1 .16 , 95 % confidence interval [CI ] = 1 .01 to 1 .33 ) and BE risk increased by 12 % (IV-OR = 1 .12 , 95 % CI = 1 .00 to 1 .25 ) per 1 kg /m (2 ) increase in BMI . BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses .People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity . These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC , and is not due to confounding or bias inherent in conventional epidemiologic analyses .

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esophageal adenocarcinoma

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