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- Title
Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma.
- Authors
van Nistelrooij, Anna M. J.; van der Korput, Hetty A. G. M.; Broer, Linda; van Marion, Ronald; van Berge Henegouwen, Mark I.; van Noesel, Carel J.; Biermann, Katharina; Spaander, Manon C. W.; Tilanus, Hugo W.; van Lanschot, J. Jan B.; Hofman, Albert; Uitterlinden, André G.; Wijnhoven, Bas P. L.; Dinjens, Winand N. M.
- 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. 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 populationbased prospective cohort study (n = 6206). Logistic regression analysis and metaanalysis 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 metaanalysis of the original GWAS and the current study revealed an improved level of significance for rs10419226 (CRTC1) (OR = 1.18, P = 6.66 × 10) and rs11789015 (BARX1) (OR = 0.83, P = 1.13 × 10). 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 makeup to the development of EAC and might contribute to gain more insight in the etiology of this cancer.
- Subjects
NETHERLANDS; SINGLE nucleotide polymorphisms; CREB protein; TREATMENT of esophageal cancer; BARRETT'S esophagus; ETIOLOGY of cancer; LOGISTIC regression analysis; CANCER genetics
- Publication
Journal of Carcinogenesis, 2015, p9
- ISSN
0974-6773
- Publication type
Article
- DOI
10.4103/14773163.157441