Language

English

Publication Date

6-1-2026

Journal

European Journal of Gastroenterology & Hepatology

PMID

41524576

Abstract

Background and aims: Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program.

Methods: We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We examined 16 single-nucleotide polymorphisms (SNPs) identified in individuals of European origin in the largest Barrett's esophagus genome-wide association study to date. We conducted a logistic regression, adjusting for age, sex, and global ancestry, to assess associations between SNPs and Barrett's esophagus/control status.

Results: Of 16 SNPs examined, logistic regression analysis showed three SNPs (rs42202, rs62217, and rs848092) were associated with Barrett's esophagus risk at Bonferroni-adjusted significance ( P < 3.1e-3) and in the same direction as previously reported. One SNP, rs2701111, met significance but showed a discordant association with Barrett's esophagus in African Americans. The association with the remaining 12 SNPs was not replicated. Effect sizes were generally larger for each SNP in our African Americans cohort.

Conclusion: This study evaluated 16 Barrett's esophagus-associated SNPs in African Americans and confirmed associations for only three Barrett's esophagus-associated variants shared across populations. The nonreplication of most loci and differences in association patterns suggest distinct genetic factors influence Barrett's esophagus in admixed populations. These findings underscore the need for discovery and replication in diverse populations.

Keywords

Humans, Barrett Esophagus, Black or African American, Polymorphism, Single Nucleotide, Case-Control Studies, Female, Genetic Predisposition to Disease, Middle Aged, Male, Genome-Wide Association Study, Aged, Genetic Loci, United States, Risk Factors, Logistic Models, Phenotype, Esophageal Neoplasms, White People, Adult

Published Open-Access

yes

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