title: ATG16L1 T300A Polymorphism is Correlated with Gastric Cancer Susceptibility.
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.
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania. buradaflorin@gmail.com.
authors.forename: Florin
authors.initials: F
authors.lastname: Burada
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania.
authors.forename: Marius Eugen
authors.initials: ME
authors.lastname: Ciurea
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania.
authors.forename: Raluca
authors.initials: R
authors.lastname: Nicoli
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Streata
authors.affiliation: Department of Surgery, University of Medicine and Pharmacy from Craiova, Petru Rares street no 2-4, 200349, Craiova, Romania.
authors.forename: Ionica Dan
authors.initials: ID
authors.lastname: Vilcea
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania.
authors.forename: Ion
authors.initials: I
authors.lastname: Rogoveanu
authors.affiliation: Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 1 May street no 66, Craiova, Romania.
authors.forename: Mihai
authors.initials: M
authors.lastname: Ioana
mesh_terms: D000368:Aged; D000071183:Autophagy-Related Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins
keywords: ATG16L1 gene; Autophagy; Gastric cancer; Gene expression; Polymorphism