@article{Gunnar Jacobs_Stephan Hellmig_Klaus Huse_Andrea Titz_Andre Franke_Ruta Kwiatkowski_Stephan Ott_Markus Kosmahl_Wolfgang Fischbach_Ralph Lucius_Wolfram Klapper_Ulrich R. Fölsch_Jochen Hampe_Stefan Schreiber_Philip Rosenstiel_2011, place={Pavia, Italy}, title={Polymorphisms in the 3′-untranslated region of the CDH1 gene are a risk factor for primary gastric diffuse large B-cell lymphoma}, volume={96}, url={https://haematologica.org/article/view/6028}, DOI={10.3324/haematol.2010.033126}, abstractNote={<strong>Background</strong> Primary gastric B-cell lymphomas arise from mucosa-associated lymphatic tissue (MALT) in patients with chronic <em>Helicobacter pylori</em> infection. We investigated whether germline variants in the <em>CDH1</em> gene, coding for E-cadherin, genetically predispose patients to primary gastric B-cell lymphoma.<strong>Design and Methods</strong> Single marker analyses of the <em>CDH1</em> 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<sup>®</sup> 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 <em>CDH1</em> 3′-untranslated region. The influence of the 3′-untranslated region on protein translation was determined by a luciferase reporter assay.<strong>Results</strong> Single marker analyses identified two single nucleotide polymorphisms in strong linkage disequilibrium located in the <em>CDH1</em> 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.<strong>Conclusions</strong> We identified variants in <em>CDH1</em> 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 <em>CDH1</em> expression. These findings support the hypothesis that besides somatic alterations of B-cells, germline variants in the <em>CDH1</em&gt; gene contribute to a predisposition to the development of primary gastric diffuse large B-cell lymphomas.}, number={7}, journal={Haematologica}, author={Gunnar Jacobs and Stephan Hellmig and Klaus Huse and Andrea Titz and Andre Franke and Ruta Kwiatkowski and Stephan Ott and Markus Kosmahl and Wolfgang Fischbach and Ralph Lucius and Wolfram Klapper and Ulrich R. Fölsch and Jochen Hampe and Stefan Schreiber and Philip Rosenstiel}, year={2011}, month={Jun.}, pages={987-995} }