Germline variations of the MALT1 gene as risk factors in the development of primary gastric B-cell lymphoma.

Hellmig, S., Bartscht, T., Fischbach, W., Ott, Stephan, Rosenstiel, Philip, Klapper, W., Folsch, U. R. and Schreiber, Stefan (2009) Germline variations of the MALT1 gene as risk factors in the development of primary gastric B-cell lymphoma. European Journal of Cancer, 45 (10). pp. 1865-1870. DOI 10.1016/j.ejca.2009.03.010.

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Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a histologically distinct tumour derived from MALT acquired as a result of Helicobacter pylori infection. The genetic susceptibility to develop primary gastric B-cell lymphoma in patients with chronic H. pylori infection is unknown. MALT1 plays a key role in malignant B-cell transformation and lymphoma progression. Thus, we investigated germline variations of MALT1 as risk factors for gastric lymphoma in a large cohort from a European multicentre study and in total 214 lymphoma patients, 593 H. pylori infected controls and 348 healthy blood donors were genotyped for four single nucleotide polymorphisms (SNPs) covering the MALT1 locus by Taqman technology. Haplotype and single marker analyses were conducted for association testing in a case-control setting. A distinct haplotype was identified that showed a trend towards protection from high-grade and low-grade lymphomas. In single marker analysis individuals homozygous for the rare allele G of SNP3 (rs12969413) were significantly protected only from gastric high-grade lymphoma compared with controls (P = 0.002, odds ratio (OR): 0.2, Wald 95% confidence interval (Cl): 0.1 < OR < 0.6). This association could not be confirmed in a second independent cohort of high-grade lymphoma patients from the Lymph node registry in Kiel (p = 0331, OR: 0.8, Wald 95% Cl: 0.4 < OR < 13). Due to the fact that SNPs 2, 3 and 4 are arranged in one LD block exhibiting nearly complete linkage disequilibrium it is rather unlikely that germline variations of MALT1 might be involved in the pathogenesis of gastric lymphoma. This is the first genetic association study that investigated polymorphisms of MALT1 as genetic risk factors in the development of primary gastric lymphoma. (C) 2009 Elsevier Ltd. All rights reserved.

Document Type: Article
Keywords: malt1gastric b-cell lymphoma; genetic susceptibility; helicobacter-pylori infection; staging classification; tissue lymphoma; bcl10 t(11/18)(q21,q21); polymorphisms; translocation activation; disease; mlt
Research affiliation: Kiel University
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
Open Access Journal?: No
DOI etc.: 10.1016/j.ejca.2009.03.010
ISSN: 0959-8049
Projects: Future Ocean
Date Deposited: 11 Feb 2011 12:16
Last Modified: 04 Jan 2017 12:11

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