We investigated if germline variations of the Topoisomerase II alpha gene could predispose patients with chronic Helicobacter pylori infection to develop gastric lymphoma and conducted a mutation detection of the entire promoter region. Single marker and haplotype analysis did not reveal any associations with development of gastric lymphoma in general, histological grade or stage of disease (P>0.05). No genetic variations in the promotor region were found in 92 chromosomes of lymphoma patients and controls and linkage disequilibrium indicated a highly conserved genomic region. The results of our work exclude genetic variations as predisposing factors of primary gastric B-cell lymphoma development.