title: Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma.
abstract: OBJECTIVE
  Recently, single nucleotide polymorphisms (SNPs) associated with esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE) were identified; rs10419226 (CRTC1), rs11789015 (BARX1), rs2687201 (FOXP1), rs2178146 (FOXF1), rs3111601 (FOXF1), and rs9936833 (FOXF1). These findings indicate that genetic susceptibility could play a role in the initiation of EAC in BE patients. The aim of this study was to validate the association between these previously identified SNPs and the risk of EAC in an independent and large case-control study.
  
  
  METHODS
  Six SNPs found to be associated with EAC and BE were genotyped by a multiplex SNaPshot analysis in 1071 EAC patients diagnosed and treated in the Netherlands. Allele frequencies were compared to a control group derived from the Rotterdam Study, a population-based prospective cohort study (n = 6206). Logistic regression analysis and meta-analysis were performed to calculate odds ratios (OR).
  
  
  RESULTS
  Rs10419226 (CRTC1) showed a significantly increased EAC risk for the minor allele (OR = 1.17, P = 0.001), and rs11789015 (BARX1) showed a significantly decreased risk for the minor allele (OR = 0.85, P = 0.004) in the logistic regression analysis. The meta-analysis of the original GWAS and the current study revealed an improved level of significance for rs10419226 (CRTC1) (OR = 1.18, P = 6.66 × 10(-10)) and rs11789015 (BARX1) (OR = 0.83, P = 1.13 × 10(-8)).
  
  
  CONCLUSIONS
  This independent and large Dutch case-control study confirms the association of rs10419226 (CRTC1) and rs11789015 (BARX1) with the risk of EAC. These findings suggest a contribution of the patient genetic make-up to the development of EAC and might contribute to gain more insight in the etiology of this cancer.
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands ; Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Anna M J
authors.initials: AM
authors.lastname: van Nistelrooij
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Hetty A G M
authors.initials: HA
authors.lastname: van der Korput
authors.affiliation: Department of Internal Medicine, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Broer
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Marion
authors.affiliation: Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Mark I
authors.initials: MI
authors.lastname: van Berge Henegouwen
authors.affiliation: Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Carel J
authors.initials: CJ
authors.lastname: van Noesel
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Manon C W
authors.initials: MC
authors.lastname: Spaander
authors.affiliation: Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.affiliation: Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: J Jan B
authors.initials: JJ
authors.lastname: van Lanschot
authors.affiliation: Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Internal Medicine, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands ; Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Bas P L
authors.initials: BP
authors.lastname: Wijnhoven
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
keywords: Barrett's esophagus; esophageal adenocarcinoma; single nucleotide polymorphisms