Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma
Journal
Journal of Clinical Oncology
Journal Volume
24
Journal Issue
21
Pages
3483-3489
Date Issued
2006
Author(s)
Lin J.-T.
Chen L.-T.
Wang T.-E.
Abstract
Purpose: 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. Patients and 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. Conclusion: 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. ? 2006 by American Society of Clinical Oncology.
SDGs
Other Subjects
CD28 antigen; cytotoxic T lymphocyte antigen 4; antiinfective agent; cytotoxic T-lymphocyte antigen 4; differentiation antigen; inducible T cell co stimulator; inducible T-cell co-stimulator; leukocyte antigen; T lymphocyte antigen; adult; article; cancer risk; cancer staging; cancer susceptibility; controlled study; female; gene; genetic polymorphism; genotype; haplotype; Helicobacter infection; Helicobacter pylori; human; inducible costimulator gene; major clinical study; male; mucosa associated lymphoid tissue lymphoma; priority journal; regulatory T lymphocyte; case control study; gene frequency; genetic polymorphism; genetics; Helicobacter infection; Helicobacter pylori; microbiology; middle aged; pathology; risk; T lymphocyte; Anti-Bacterial Agents; Antigens, CD; Antigens, CD28; Antigens, Differentiation; Antigens, Differentiation, T-Lymphocyte; Case-Control Studies; Female; Gene Frequency; Genotype; Haplotypes; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, Mucosa-Associated Lymphoid Tissue; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; T-Lymphocytes
Type
journal article