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 single nucleotide polymorphisms (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 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. 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.
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 single nucleotide polymorphisms (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 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. 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.
Authors: N A C S Wong; J Wilding; S Bartlett; Y Liu; B F Warren; J Piris; N Maynard; R Marshall; W F Bodmer Journal: Proc Natl Acad Sci U S A Date: 2005-05-13 Impact factor: 11.205
Authors: L M G Moons; D A Bax; E J Kuipers; H Van Dekken; J Haringsma; A H M Van Vliet; P D Siersema; J G Kusters Journal: J Clin Pathol Date: 2004-10 Impact factor: 3.411
Authors: Chantal A Ten Kate; Annelies de Klein; Bianca M de Graaf; Michail Doukas; Antti Koivusalo; Mikko P Pakarinen; Robert van der Helm; Tom Brands; Hanneke IJsselstijn; Yolande van Bever; René M H Wijnen; Manon C W Spaander; Erwin Brosens Journal: Cancers (Basel) Date: 2022-01-20 Impact factor: 6.639