TY - JOUR AU - Gunnar Jacobs, AU - Stephan Hellmig, AU - Klaus Huse, AU - Andrea Titz, AU - Andre Franke, AU - Ruta Kwiatkowski, AU - Stephan Ott, AU - Markus Kosmahl, AU - Wolfgang Fischbach, AU - Ralph Lucius, AU - Wolfram Klapper, AU - Ulrich R. Fölsch, AU - Jochen Hampe, AU - Stefan Schreiber, AU - Philip Rosenstiel, PY - 2011/06/30 Y2 - 2024/03/28 TI - Polymorphisms in the 3′-untranslated region of the CDH1 gene are a risk factor for primary gastric diffuse large B-cell lymphoma JF - Haematologica JA - haematol VL - 96 IS - 7 SE - Articles DO - 10.3324/haematol.2010.033126 UR - https://haematologica.org/article/view/6028 SP - 987-995 AB - Background Primary gastric B-cell lymphomas arise from mucosa-associated lymphatic tissue (MALT) in patients with chronic Helicobacter pylori infection. We investigated whether germline variants in the CDH1 gene, coding for E-cadherin, genetically predispose patients to primary gastric B-cell lymphoma.Design and Methods Single marker analyses of the CDH1 gene were conducted in patients with primary gastric B-cell lymphoma (n=144), in patients with primary gastric high-grade lymphoma (n=61), and in healthy blood donors (n=361). Twelve single nucleotide polymorphisms were genotyped by TaqMan® technology. Allelic imbalance was tested by pyrosequencing and clone direct sequencing of heterozygote genomic and cDNA. Mutation detection was conducted around the poly-A signal of the CDH1 3′-untranslated region. The influence of the 3′-untranslated region on protein translation was determined by a luciferase reporter assay.Results Single marker analyses identified two single nucleotide polymorphisms in strong linkage disequilibrium located in the CDH1 3′-untranslated region. One of them was significantly associated with primary gastric diffuse large B-cell lymphomas after correction for multiple testing and this association was confirmed in an independent sample set. Patients homozygous for the rare T allele (rs1801026) had a 4.9-fold increased risk (95% CI: 1.5–15.9) of developing primary gastric diffuse large B-cell lymphoma. Allelic imbalance and reporter gene assays indicated a putative influence on mRNA stability and/or translational efficacy.Conclusions We identified variants in CDH1 as the first potential genetic risk factors for the development of primary gastric diffuse large B-cell lymphomas. One of the potentially causative variants affects allelic CDH1 expression. These findings support the hypothesis that besides somatic alterations of B-cells, germline variants in the CDH1 gene contribute to a predisposition to the development of primary gastric diffuse large B-cell lymphomas. ER -