title: Single nucleotide polymorphisms of caudal type homeobox 1 and 2 are associated with Barrett's esophagus.
abstract: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, NC, 27707, USA, rendrjxau@hotmail.com.
authors.forename: Dongren
authors.initials: D
authors.lastname: Ren
authors.forename: Gaolin
authors.initials: G
authors.lastname: Zheng
authors.forename: Susan
authors.initials: S
authors.lastname: Bream
authors.forename: Whitney
authors.initials: W
authors.lastname: Tevebaugh
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics*; D000071616:CDX2 Transcription Factor; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006551:Hernia, Hiatal / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D055815:Young Adult
chemical_list: C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins
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