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. To determine associations between Cdx1 and Cdx2 single nucleotide polymorphisms (SNPs) and BE. Genomic DNA was extracted from blood samples collected from BE (n = 109) and GERD (n = 223) patients for genotyping of 5 SNPs each of Cdx1 and Cdx2 using TaqMan allelic discrimination assays. Odds ratios and 95 % confidence intervals 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. Older age (a parts per thousand yen50 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). 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.