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ATG16L1 T300A Polymorphism is Correlated with Gastric Cancer Susceptibility

  • Original Article
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Pathology & Oncology Research

Abstract

Gastric cancer is a major leading cause of cancer-related death in both sexes in Europe. The role of autophagy process in carcinogenesis remains unclear and there is increasing evidence that Helicobacter pylori is a key player in modulating autophagy in gastric carcinogenesis. The aim of this study was to assess the potential association of ATG16L1 T300A polymorphism with susceptibility of gastric cancer, and further to analyze the expression profile of ATG16L1 gene in paired tumoral and peritumoral gastric tissue. A total of 108 patients diagnosed with gastric cancer and 242 healthy controls were enrolled. ATG16L1 T300A polymorphism was detected using TaqMan genotyping assay containing primers and specific probes for A and G allele, respectively. ATG16L1 mRNA level was evaluated in 34 paired tumoral and peritumoral tissues using qRT-PCR. We found a significant association for both carriers of AG (OR 0.52, 95 % CI: 0.30–0.91, p = 0.02) and GG genotype (OR 0.53, 95 % CI: 0.28–0.98, p = 0.043), these were at a lower risk for gastric cancer when compared with the wild-type AA genotype. The strongest association was observed in a dominant model, the carriers of G allele were protected against gastric cancer (OR 0.52, 95 % CI: 0.13–0.88, p = 0.013). In a stratified analyse, the association was limited to non-cardia type and intestinal type. ATG16L1 gene expression was detected in both tumor and peritumoral tissues, with the mRNA-ATG16L1 levels significantly higher in tumor sample. Our results suggest that ATG16L1 T300A polymorphism may be associated with gastric carcinogenesis.

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Acknowledgments

F.B. was supported by Grant POSDRU/159/1.5/S/133377, from European Social Found, Human Resources Development Operational Programme 2007-2013.

Author Contributions

F.B., I.R. and M.I. conceived the study; F.B, R.N. and I.S. performed the experiments; E.M.C., I.D.V., I.R. and I.M. provided resource and materials; F.B, E.M.C., I.S., R.N., and I.D.V analyzed the data; F.B., E.M.C. and I.M. wrote the manuscript; I.R. and I.M. supervised the project.

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Authors and Affiliations

  1. Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania

    Florin Burada, Marius Eugen Ciurea, Raluca Nicoli, Ioana Streata, Ion Rogoveanu & Mihai Ioana

  2. Department of Surgery, University of Medicine and Pharmacy from Craiova, Petru Rares street no 2-4, 200349, Craiova, Romania

    Ionica Dan Vilcea

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  1. Florin Burada
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  2. Marius Eugen Ciurea
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  3. Raluca Nicoli
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Correspondence to Florin Burada.

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The authors declare that they have no conflict of interest.

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Florin Burada and Marius Eugen Ciurea contributed equally to this article.

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Burada, F., Ciurea, M.E., Nicoli, R. et al. ATG16L1 T300A Polymorphism is Correlated with Gastric Cancer Susceptibility. Pathol. Oncol. Res. 22, 317–322 (2016). https://doi.org/10.1007/s12253-015-0006-9

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  • DOI: https://doi.org/10.1007/s12253-015-0006-9

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