title: Gastric marginal zone lymphoma is associated with polymorphisms in genes involved in inflammatory response and antioxidative capacity.
abstract: Gastric marginal zone lymphoma (GMZL) is strongly associated with Helicobacter pylori infection, which induces a chronic inflammatory response. Inflammation can result in DNA damage related to its severity, the cellular antioxidant capacity, and the integrity of DNA repair mechanisms. Interleukin-1 (IL-1) polymorphisms have been shown to be important mediators of inflammation, while glutathione S-transferase GST T1 and GST M1 polymorphisms are believed to affect cellular antioxidant capacity. We aimed to determine whether polymorphisms at the IL-1 and GST T1 and GST M1 loci modulate the risk of developing GMZL. Blood and biopsy samples were obtained for a historical series of 66 GMZL cases, whereas blood samples were available from 163 healthy controls. Genotypes were obtained for GST T1, GST M1, IL-1 RN, and IL-1B-31 using PCR-based techniques. H pylori infection was found in 86.0% of cases, whereas in the control population only 37.4% tested positive. The IL-1 RN 2/2 genotype was significantly associated with risk of GMZL (odds ratio [OR], 5.51; 95% confidence interval [CI] 2.16-14.07), but not the IL-1B-31 genotype. Likewise, the GST T1 null genotype was strongly associated with risk of GMZL (OR, 9.51; 95% CI 4.57-19.81), but not the GST M1 genotype. Evidence was found of effect modification between the IL-1 RN and GST T1 genotypes (P =.02). The combination of the IL-1 RN 2/2 and GST T1 null genotype was most strongly associated with risk of GMZL (OR, 32.29; 95% CI 6.92-150-63). These results support the hypothesis that the risk of developing GMZL is influenced by inter-individual variation in the cellular inflammatory immune responses to H pylori infection, and to antioxidative capacity.
authors.affiliation: Epidemiology and Genetics Unit, University of Leeds, Leeds, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Rollinson
authors.forename: Adam P
authors.initials: AP
authors.lastname: Levene
authors.forename: Fiona K
authors.initials: FK
authors.lastname: Mensah
authors.forename: Philippa L
authors.initials: PL
authors.lastname: Roddam
authors.forename: James M
authors.initials: JM
authors.lastname: Allan
authors.forename: Tim C
authors.initials: TC
authors.lastname: Diss
authors.forename: Eve
authors.initials: E
authors.lastname: Roman
authors.forename: Andrew
authors.initials: A
authors.lastname: Jack
authors.forename: Kenneth
authors.initials: K
authors.lastname: MacLennan
authors.forename: Michael F
authors.initials: MF
authors.lastname: Dixon
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants; D016022:Case-Control Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000382:microbiology; D018836:Inflammation Mediators; D007375:Interleukin-1 / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology* / Q000235:genetics / Q000382:microbiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics / Q000382:microbiology
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D007375:Interleukin-1; D005982:Glutathione Transferase