Polymorphisms in the 3'-untranslated region of the CDH1 gene are a risk factor for primary gastric diffuse large B-cell lymphoma

Haematologica. 2011 Jul;96(7):987-95. doi: 10.3324/haematol.2010.033126. Epub 2011 Apr 1.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Adult
  • Aged
  • Antigens, CD
  • Cadherins / genetics*
  • Female
  • Gene Order
  • Genetic Association Studies
  • Genetic Loci
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Non-Hodgkin / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • RNA Stability / genetics
  • Risk Factors
  • Stomach Neoplasms / genetics*


  • 3' Untranslated Regions
  • Antigens, CD
  • CDH1 protein, human
  • Cadherins

Supplementary concepts

  • Familial primary gastric lymphoma