Single Nucleotide Polymorphisms of Caudal Type Homeobox 1 and 2 Are Associated with Barrett’s Esophagus

BACKGROUND: Barrett’s esophagus (BE), the premalignant lesion of esophageal adenocarcinoma, is believed to develop as a result of chronic gastroesophageal reflux disease (GERD). Approximately 10% of subjects with GERD progress to BE. Genetic, epigenetic and other risk factors may contribute to this inter-individual variability. Caudal type homeobox 1 (Cdx1) and Caudal type homeobox 2 (Cdx2) play important regulatory roles in the development of human BE. AIMS: To determine associations between Cdx1 and Cdx2 SNPs and BE METHODS: Genomic DNA was extracted from blood samples collected from BE (n = 109) and GERD (n = 223) patients for genotyping of 5 single nucleotide polymorphisms (SNPs) each of Cdx1 and Cdx2 using TaqMan allelic discrimination assays. Odds ratios (OR) and 95% confidence intervals (CI) of SNPs and haplotypes were calculated with a logistic regression model adjusted for factors including age, sex and hiatal hernia. Interactions between genetic variants and these three risk factors were also analyzed. RESULTS: Older age ( 50 years), male sex and hiatal hernia were significantly associated with BE (P < 0.001). Five variants of Cdx1 SNPs (rs3776082, rs717746 and rs3776083), one Cdx1 haplotype, and three variants of Cdx2 SNPs (rs4769585 and rs3812863) were associated with BE (P < 0.05). Statistically significant interactions were detected between most of these SNPs and the three risk factors (P < 0.05). CONCLUSION: Certain SNPs of Cdx1 and Cdx2 and their interactions with other risk factors are associated with BE, and may contribute to human susceptibility to BE