Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma
Journal
Blood Cancer Journal
Journal Volume
4
Journal Issue
10
Pages
exx
Date Issued
2014
Author(s)
Liao F.
Hsu Y.-C.
Yang Y.-C.
Chen J.-P.
Chen L.-T.
Fann C.S.J.
Lin J.-T.
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 (r2 = 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, RegIII' 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, Po<.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. ? 2014 Macmillan Publishers Limited All rights reserved.
SDGs
Other Subjects
chemokine; cytokine; interleukin 22; neutrophil gelatinase associated lipocalin; interleukin derivative; interleukin-22; tumor protein; Article; CD4+ T lymphocyte; cellular immunity; controlled study; disease association; disease predisposition; epithelium cell; female; gene linkage disequilibrium; genetic association; genetic polymorphism; genetic predisposition; genotype; Helicobacter pylori; human; major clinical study; male; marginal zone lymphoma; mononuclear cell; protein expression; risk assessment; single nucleotide polymorphism; stomach lymphoma; treatment response; biosynthesis; clinical trial; gene expression regulation; genetic predisposition; genetics; Helicobacter Infections; Helicobacter pylori; Lymphoma, B-Cell, Marginal Zone; metabolism; microbiology; multicenter study; randomized controlled trial; single nucleotide polymorphism; Stomach Neoplasms; tumor cell line; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Interleukins; Lymphoma, B-Cell, Marginal Zone; Male; Neoplasm Proteins; Polymorphism, Single Nucleotide; Stomach Neoplasms
Publisher
Nature Publishing Group
Type
journal article