Gastric Marginal Zone Lymphoma Is Associated With Polymorphisms In Genes Involved In Inflammatory Response And Anti-Oxidative Capacity

Gastric marginal zone lymphoma (GMZL) is strongly associated with Helicobacter pylori (H. pylori) infection, which induces an inflammatory response, subsequently resulting in the generation of DNA-damaging reactive oxygen species (ROS). The extent of damage will depend upon the severity of inflammation, the cellular antioxidant capacity, and the integrity of cellular DNA repair mechanisms. Interleukin-1 (IL-1) gene cluster polymorphisms have been shown to be important mediators of inflammation, while polymorphisms in the glutathione S-transferase GST T1 and GST M1 genes 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. Archived peripheral blood and biopsy samples were collected for a historical series of 66 GMZL cases; while blood samples from 163 healthy controls were collected for use as a comparison series. Genotypes were determined for GST T1, GST M1, IL-1 RN, and IL-IB-31 using PCR based techniques. For the cases where H. pylori status could be determined, infection was found in 86.0%, while the prevalence of H. pylori infection in the control population was found to be 37.4%. The IL1 RN genotype was significantly associated with risk of GMZL, (OR 5.51, 95% CI 2.16-14.07) for the IL-1 RN 2/2 genotype compared to the IL-1 RN 1/1. The IL-1B-31 genotype was not associated with GMZL risk. The GST T1 null genotype was strongly associated with risk of GMZL (OR 9.51, 95% CI 4.57-19.81), whereas the GST M1 null genotype was not associated with risk of GMZL. Evidence was found of effect modification between the IL-1 RN, and GST T1 genotypes (p=0.02). The combination of 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). IThese results support the hypothesis that the risk of developing GMZL is influenced by inter-individual variation in inflammatory response, modulating the immune response to H. pylori infection, and anti-oxidative capacity determining the body’s ability to detoxify ROS generated in the immune response. For personal use only. on October 17, 2017. by guest www.bloodjournal.org From