Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation

Int J Cancer. 2006 Dec 15;119(12):2970-3. doi: 10.1002/ijc.22280.

Abstract

The NBS1 gene mutation, 657del5, frequent in the Slavic populations of Central Europe, is found in most patients with Nijmegen breakage syndrome (NBS), a recessive autosomal disorder with a very high incidence of non-Hodgkin lymphoma (NHL). We have previously described 2 heterozygous 657del5 mutation carriers among 42 adult NHL probands from Central Poland. Here we report 6 additional carriers of the 657del5 mutation and 2 carriers of the pathogenic NBS1 R215W mutation, among 186 other NHL patients also from Central Poland. The 657del5 carrier frequency in the pooled group of these 228 patients was significantly higher than in population controls (OR 5.85, 95% CI: 2.29-15.00, p = 0.0001). Interestingly, 4 of these carriers were found among 37 patients with gastrointestinal lymphoma (OR 19.52, 95% CI: 5.82-65.42, p = 0.0002). These findings imply that heterozygous NBS1 germline mutations may contribute significantly to the overall incidence of NHL, especially of the gastrointestinal tract, in Central Europe.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle Proteins / genetics*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / pathology*
  • Gene Frequency
  • Germ-Line Mutation / genetics
  • Heterozygote
  • Humans
  • Lymphoma / classification
  • Lymphoma / genetics
  • Lymphoma / pathology*
  • Lymphoma, Non-Hodgkin / genetics
  • Lymphoma, Non-Hodgkin / pathology
  • Middle Aged
  • Mutation / genetics*
  • Mutation, Missense / genetics
  • Nuclear Proteins / genetics*
  • Odds Ratio
  • Poland
  • Risk Factors
  • Sequence Deletion

Substances

  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins