title: Polymorphisms of death pathway genes FAS and FASL and risk of premalignant gastric lesions.
abstract: BACKGROUND
  Tumorigenesis is a multistep process that begins with the abrogation of normal controls of apoptosis and cell proliferation, and the FAS receptor-ligand system is a key regulator of apoptosis. The aim of this study was to investigate whether functional polymorphisms of death pathway genes (FAS and FASL) are associated with the development of gastric atrophy and intestinal metaplasia.
  
  
  METHODS
  Genotypes in the promoter regions of the FAS (-1377G/A and -670A/G) and FASL (-844T/C) genes of 101 healthy individuals and 86 gastric cancer patients were determined by PCR-RFLP. Additionally, gastric histological changes were examined according to the updated Sydney System.
  
  
  RESULTS
  The carriage of FASL -844C allele significantly increased the risk of atrophy in the gastric corpus, with an adjusted odds ratio (OR) of 5.0 [95% confidence interval (CI), 1.5-6.8]. There were no gene-gene interactions among FASL -844T/C, FAS -1377G/A and FAS -670A/G polymorphisms in developing premalignant gastric lesions. In the 109 individuals with Helicobacterpylori infection, carrying the FAS -1377A allele was a protective factor for developing intestinal metaplasia in the antrum (OR, 0.3; 95% CI, 0.1-0.9), while carrying the FASL -844C allele was a risk factor for developing gastric atrophy in the corpus (OR, 9.4; 95% CI, 1.7-53.4).
  
  
  CONCLUSIONS
  FAS and FASL genotypes of the hosts are important determinants in the pathogenesis of gastric atrophy and intestinal metaplasia in H. pylori-infected individuals.
authors.affiliation: Division of Gastroenterology and General Medicine, Department of Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan, R.O.C. williamhsup@yahoo.com.tw
authors.forename: Ping-I
authors.initials: PI
authors.lastname: Hsu
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.forename: E-Ming
authors.initials: EM
authors.lastname: Wang
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
authors.forename: Gin-Ho
authors.initials: GH
authors.lastname: Lo
authors.forename: Feng-Woei
authors.initials: FW
authors.lastname: Tsay
authors.forename: Tai-An
authors.initials: TA
authors.lastname: Chen
authors.forename: Hsiao-Bai
authors.initials: HB
authors.lastname: Yang
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Chen
authors.forename: Weir-Sen
authors.initials: WS
authors.lastname: Lin
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Lai
mesh_terms: D000368:Aged; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics* / Q000382:microbiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor