Causal relationships between dietary habits and Barrett's Esophagus risk: A Univariable and Multivariable Mendelian Randomization Study

Aims: Dietary habits are reported to be associated with Barrett's esophagus (BE) risk; however, whether there is a causal relationship remains controversial. Here, we systematically examined the causal effects of genetically predicted dietary habits on BE risk through a Mendelian randomization (MR) analysis approach. Methods: Data for exposures were obtained from the UK Biobank (UKB), while the summary-level data for outcomes were obtained from a large sample-size GWAS meta-analysis. Genetic variants associated with 17 ordinary dietary habits at the genome-wide significance level were regarded as instrumental variables (IVs). Univariable and multivariable MR analyses were conducted to explore the causal relationships between dietary habits and BE risk. Sensitivity analyses were implemented to evaluate robustness of the results and determine the potential pleiotropy bias. Results: Univariable MR (UVMR) analysis showed that genetic predisposition to alcohol intake frequency, cooked vegetable intake, beef intake, bread intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake were associated with BE risk, with all P values <0.05. After adjusting confounders, the effects of four dietary habits on BE risk persisted; multivariable MR (MVMR) analysis revealed that alcohol intake frequency (adjusted odds ratio (OR) = 1.74 (1.34, 2.27); P = 3.42 × 10-5) was causally associated with higher BE risk, the cooked vegetable intake (adjusted OR = 2.64 (1.16, 5.97); P = 0.02) had suggestively increased BE risk, while higher consumption of bread (adjusted OR = 0.54 (0.32-0.91); P = 0.02) and fresh fruit (adjusted OR = 0.34 (0.15, 0.77); P = 0.01) were suggestively associated with lower BE risk. Conclusions: These MR analyses demonstrate evidence of causal relationships between dietary habits and BE risk. These findings provide new insights into targeted dietary intervention strategies for BE prevention.