Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma.
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.
Cheng
Tsu-Yao
TY
Department of Laboratory Medicine, Division of Gastroenterology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Lin
Jaw-Town
JT
Chen
Li-Tzong
LT
Shun
Chia-Tung
CT
Wang
Hsiu-Po
HP
Lin
Ming-Tsang
MT
Wang
Tsang-En
TE
Cheng
Ann-Lii
AL
Wu
Ming-Shiang
MS
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
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