title: Autophagy in Helicobacter pylori Infection and Related Gastric Cancer.
abstract: BACKGROUND
  Autophagy, a degradation pathway in which cytoplasmic content is engulfed and degraded by lysosomal hydrolases, plays a pivotal role in infection and inflammation. Given that defects in autophagy lead to increased susceptibility to infection, we investigated the role of autophagy in Helicobacter pylori-related gastric cancer (GC).
  
  
  METHODS
  Gene expression of 84 molecules was examined through quantitative real-time PCR in gastric epithelial cells (AGS) and macrophages (THP-1) upon exposure to H. pylori GC026 (GC) and 26695 (gastritis). Further, ATG16L1 rs2241880, IRGM rs13361189, and IRGM rs4958847, polymorphisms that have been investigated in relation to H. pylori infection or GC in Caucasians, were detected by MALDI-TOF mass spectrometry in 304 ethnic Chinese (86 noncardia GC cases/218 functional dyspepsia controls).
  
  
  RESULTS
  Gene expression analyses showed twenty-eight molecules involved in vesicle nucleation, elongation, and maturation to be significantly down-regulated in H. pylori GC026-challenged AGS cells. Further, core autophagy proteins and autophagy regulators were differentially expressed in H. pylori-challenged THP-1-derived macrophages. Analyses of the selected polymorphisms showed that ATG16L1 rs2241880 increased the risk of GC (OR: 2.38, 95% CI: 1.34-4.24) and H. pylori infection (OR: 1.49, 95% CI: 1.02-2.16) while IRGM rs4958847 decreased GC risk (OR: 0.26, 95% CI: 0.09-0.74) in ethnic Chinese, these effect sizes being especially strong in H. pylori-infected individuals (ATG16L1 rs2241880 and IRGM rs13361189).
  
  
  CONCLUSIONS
  Our findings indicate that highly virulent H. pylori strains markedly modulate autophagy in the host cell. Further, for the first time, autophagy polymorphisms were associated with GC in Chinese, a high GC-risk population.
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors: Natalia
authors: N
authors: Castaño-Rodríguez
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors: Nadeem O
authors: NO
authors: Kaakoush
authors: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Khean-Lee
authors: KL
authors: Goh
authors: Division of Gastroenterology, Department of Medicine, Changi General Hospital, Singapore City, Singapore.
authors: Kwong Ming
authors: KM
authors: Fock
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors: Hazel M
authors: HM
authors: Mitchell
mesh_terms: D000328:Adult; D000368:Aged; D001343:Autophagy; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005006:Ethnicity; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications* / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
keywords: Helicobacter pylori; autophagy; gene expression; polymorphism; stomach neoplasm