Interleukin-10 (-819 C/T) and TNF-A (-308 G/A) as Risk Factors for H. pylori-Associated Gastric MALT-Lymphoma

Abstract

With great interest we read the article by Achyut et al. about the influence of genetic variants in the promoter region of the Interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-A) gene on gastritis and lymphoid follicle development in patients with H. pylori infection [1]. The authors genotyped 130 patients with non-ulcer dyspepsia (NUD) and 200 healthy age-matched controls for IL-10 (-819) and TNF-A (-308). They found that carriers of the TNF-A (-308) A allele had a more than twofold increased risk of lymphoid follicle formation. It is generally accepted that the presence of lymphoid follicles and mucosa associated lymphatic tissue (MALT) is solely a sequelae of H. pylori infection [2,3]. Pro-inflammatory genetic polymorphisms may influence the histological degree of mucosal inflammation [4] which may vary according to the localization of the biopsy. To identify a robust association of germline polymorphisms with the outcome of H. pylori infection, unambiguous phenotypes such as ulcer disease, gastric carcinoma, or primary gastric B-cell lymphoma are needed. Immediately, the question arises if these two polymorphisms constitute risk factors for the development of H. pylori-associated gastric MALT-lymphoma. In a previous study we investigated the association of four TNF-A promoter polymorphisms with gastric lymphoma [5]. Carriers of the rare allele T of TNF-A (-857) had a significantly increased risk to develop primary lowand high-grade lymphoma. TNF-A (-308) did not show any association signal. To our knowledge IL-10 (-819) has never been tested for association with gastric MALT lymphoma. Thus, we genotyped IL-10 (-819) in a sample of 363 healthy blood donors, 88 patients with primary gastric low-grade lymphoma (MALT) from a large European multicenter study [6] and 342 H. pylori-infected patients without MALTlymphoma (Table 1). There was no difference in allele and genotype distribution between the three groups. In a preceding study we could show that IL-10 promoter haplotypes do not confer a risk factor for gastric ulcer in H. pylori infection as well [7]. When comparing the results of genetic association studies, the ethnic background of the study population has to be taken into consideration. Prevalence of the rare allele A of TNF-A (-308) was 16.0% in our healthy blood donors and 10.7% in the Indian control group. The prevalence of the rare allele T of IL-10 (-819) was 22.5% in our healthy blood donors and 35.7% in the Indian control group, respectively. In conclusion, there is no evidence that IL-10 (-819) and TNF-A (-308) confer genetic risk factors for H. pylori-associated gastric MALT lymphoma, at least in Caucasian individuals. Table 1 shows genotype frequencies of IL-10 (-819 C/T) and TNF-A (-308) in healthy blood donors, H. pyloriinfected individuals, and gastric MALT-lymphoma patients. Susceptibility to infection was tested by comparing genotype frequencies of blood donors and H. pylori-infected individuals and susceptibility to MALT-lymphoma was S. Hellmig (&) T. Bartscht U. R. Folsch Department of General Internal Medicine, University Hospital Schleswig-Holstein, Schittenhelmstr. 12, 24105 Kiel, Germany e-mail: shellmig@1med.uni-kiel.de