ORIGINAL ARTICLE
Year : 2015  |  Volume : 14  |  Issue : 1  |  Page : 5

Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma


1 Department of Pathology; Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands
2 Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands
3 Department of Internal Medicine, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands
4 Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands
5 Department of Pathology, Academic Medical Centre, Amsterdam, Netherlands
6 Department of Gastroenterology and Hepatology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands
7 Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands
8 Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands
9 Department of Internal Medicine; Department of Epidemiology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam, Netherlands

Correspondence Address:
Winand N. M. Dinjens
Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre, Rotterdam
Netherlands
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Source of Support: This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam., Conflict of Interest: None


DOI: 10.4103/1477-3163.157441

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.


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