title: Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma.
abstract: Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: F
authors.initials: F
authors.lastname: Liao
authors.affiliation: 1] Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan [2] Center for Database Research, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kuo
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: J-P
authors.initials: JP
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: P-N
authors.initials: PN
authors.lastname: Hsu
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: C-W
authors.initials: CW
authors.lastname: Lin
authors.affiliation: National Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan.
authors.forename: L-T
authors.initials: LT
authors.lastname: Chen
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: A-L
authors.initials: AL
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: C S J
authors.initials: CS
authors.lastname: Fann
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: J-T
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: M-S
authors.initials: MS
authors.lastname: Wu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D016480:Helicobacter pylori; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000628:therapy; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000628:therapy; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D009363:Neoplasm Proteins; D000097043:Interleukin-22