Anna M. J. van Nistelrooij1, Hetty A. G. M. van der Korput2, Linda Broer3, Ronald van Marion2, Mark I van Berge Henegouwen4, Carel J van Noesel5, Katharina Biermann2, Manon C. W. Spaander6, Hugo W Tilanus7, J Jan B. van Lanschot7, Albert Hofman8, André G Uitterlinden9, Bas P. L. Wijnhoven7, Winand N. M. Dinjens2
1Department of Pathology; Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
2Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
3Department of Internal Medicine, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
4 Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands.
5Department of Pathology, Academic Medical Centre, Amsterdam, Netherlands.
6Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
7Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
8Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
9Department of Internal Medicine; Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands.
DOI: 10.4103/1477-3163.157441
ABSTRACT
Objective: Recently, single nucleotide polymorphisms (SNPs) associated with esophageal adenocarcinoma (EAC) and Barrett’s esophagus (BE) were identified; rs10419226 (CRTC10), rs11789015 (BARX1), rs2687201 (FOXP10), rs2178146 (FOXF1), rs3111601 (FOXF10), 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. Design: 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.
Keywords: Barrett′s esophagus, esophageal adenocarcinoma, single nucleotide polymorphisms