title: Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma.
abstract: OBJECTIVE
  Helicobacter pylori infection and host susceptibility interact to develop gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and activation of specific T cells might play a crucial role in this process. Recent investigations show that the CTLA4, CD28, and ICOS genes are located on chromosome 2q33 and their polymorphisms confer susceptibility to infectious and immune diseases through deregulation of T-cell stimulation. We aimed to determine the role of CTLA4, CD28, and ICOS polymorphisms in gastric MALT lymphoma.
  
  
  METHODS
  Genotyping for CTLA4 (49 A/G, -318 C/T, and CT60 A/G), CD28 (IVS3+ 17T/C), and ICOS (c.602 A/C and c.1624C/T) was performed for 62 patients with gastric MALT lymphoma and compared with 250 unrelated healthy controls.
  
  
  RESULTS
  H pylori infection was significantly higher in patients with gastric MALT lymphoma (90.3%) compared with controls (66.4%; P < .001). The CTLA4 -318 C/T genotype was associated with a lower risk of developing gastric MALT lymphoma (odds ratio [OR] = 0.3; P = .022), whereas CTLA4 49 G/G genotype was linked to a higher risk (OR = 4.1; P = .044). In patients with H pylori infection, CTLA4 49 G/G genotype was associated with an even higher risk (OR = 6.4; P = .047). Carriage of the tightly linked -318C -49G haplotype conferred a four-fold higher susceptibility to MALT lymphoma (OR = 4.2; P = .042). Complete remission after H pylori eradication was related to tumor stage but not to genotypes or haplotypes.
  
  
  CONCLUSIONS
  These results indicate a genetic link of CTLA4 gene polymorphisms to development of gastric MALT lymphoma and indirectly support the crucial role of host activated T cells in the MALT lymphomagenesis.
authors.affiliation: Department of Laboratory Medicine, Division of Gastroenterology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tsu-Yao
authors.initials: TY
authors.lastname: Cheng
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Hsiu-Po
authors.initials: HP
authors.lastname: Wang
authors.forename: Ming-Tsang
authors.initials: MT
authors.lastname: Lin
authors.forename: Tsang-En
authors.initials: TE
authors.lastname: Wang
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D018106:CD28 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D016481:Helicobacter Infections / Q000150:complications* / Q000188:drug therapy; D016480:Helicobacter pylori; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein