title: STAT3 polymorphism and Helicobacter pylori CagA strains with higher number of EPIYA-C segments independently increase the risk of gastric cancer.
abstract: BACKGROUND
  Because to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer.
  
  
  METHODS
  We included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model.
  
  
  RESULTS
  The rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p < 0.001; OR = 3.01; 95 % CI = 2.29-3.98). When stimulated with LPS (lipopolysaccharide) or Pam3Cys, peripheral mononuclear cells of healthy carriers of the rs744166 GG and AG genotypes expressed higher levels of STAT3 mRNA than those carrying AA genotype (p = 0.04 for both). The nuclear expression of phosphorylated p-STAT3 protein was significantly higher in the antral gastric tissue of carriers of rs744166 GG genotype than in carriers of AG and AA genotypes.
  
  
  CONCLUSIONS
  Our study provides evidence that STAT3 rs744166 G allele and infection with CagA-positive H. pylori with higher number of EPIYA-C segments are independent risk factors for gastric cancer. The odds ratio of having gastric cancer was greater when bacterium and host high risk genotypes were combined.
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. garocha@medicina.ufmg.br.
authors.forename: Gifone A
authors.initials: GA
authors.lastname: Rocha
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. andreia@medicina.ufmg.br.
authors.forename: Andreia M C
authors.initials: AM
authors.lastname: Rocha
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. adrianadiasgomes@yahoo.com.br.
authors.forename: Adriana D
authors.initials: AD
authors.lastname: Gomes
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. cesarfariajr@gmail.com.
authors.forename: César Ll
authors.initials: CL
authors.lastname: Faria
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. freiremelo@yahoo.com.br.
authors.forename: Fabrício F
authors.initials: FF
authors.lastname: Melo
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. sergiobatistamg@gmail.com.
authors.forename: Sérgio A
authors.initials: SA
authors.lastname: Batista
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. cfernandes.viviane@gmail.com.
authors.forename: Viviane C
authors.initials: VC
authors.lastname: Fernandes
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. nathaliebfa@hotmail.com.
authors.forename: Nathálie B F
authors.initials: NB
authors.lastname: Almeida
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. kadnayt@yahoo.com.br.
authors.forename: Kádima N
authors.initials: KN
authors.lastname: Teixeira
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. britoks@hotmail.com.
authors.forename: Kátia S
authors.initials: KS
authors.lastname: Brito
authors.affiliation: Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190 s/216, 30130-100, Belo Horizonte, Brazil. dqueiroz@medicina.ufmg.br.
authors.forename: Dulciene Maria Magalhães
authors.initials: DM
authors.lastname: Queiroz
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000097:blood / Q000235:genetics*; D001426:Bacterial Proteins / Q000097:blood / Q000235:genetics*; D015415:Biomarkers; D005260:Female; D005756:Gastritis / Q000235:genetics / Q000382:microbiology*; D056726:Genetic Association Studies; D016481:Helicobacter Infections / Q000097:blood / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C080866:cagA protein, Helicobacter pylori