gms | German Medical Science

MAINZ//2011: 56. GMDS-Jahrestagung und 6. DGEpi-Jahrestagung

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V.
Deutsche Gesellschaft für Epidemiologie e. V.

26. - 29.09.2011 in Mainz

Polymorphisms in DNA repair genes modify lymphoma risk

Meeting Abstract

  • Katja Butterbach - German Cancer Research Center, Heidelberg
  • Odilia Popanda - German Cancer Research Center, Heidelberg
  • Silvia de Sanjosé - Institut Català d' Oncologia, Barcelona
  • Yolanda Benavente - Institut Català d' Oncologia, Barcelona
  • Nikolaus Becker - German Cancer Research Center, Heidelberg
  • Lenka Foretova - Masaryk Memorial Cancer Institute, Brno
  • Marc Maynadie - EA4184 University of Burgundy, Dijon
  • Pierluigi Cocco - University of Cagliari, Cagliari
  • Anthony Staines - Dublin City University, Dublin
  • Rudolf Kaaks - German Cancer Research Center, Heidelberg
  • Stefanie Hieke - Institute of Medical Biometry and Medical Informatics, Freiburg
  • Martin Schumacher - Institute of Medical Biometry and Medical Informatics, Freiburg
  • Paolo Boffetta - The Tisch Cancer Institute, Mount Sinai School of Medicine, NewYork
  • Paul Brennan - International Agency for Research on Cancer, Lyon
  • Alexandra Nieters - Centre of Chronic Immunodeficiency, University Medical Center and University of Freiburg, Freiburg

Mainz//2011. 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi). Mainz, 26.-29.09.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11gmds226

doi: 10.3205/11gmds226, urn:nbn:de:0183-11gmds2269

Published: September 20, 2011

© 2011 Butterbach et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Introduction: The high risk of lymphoma among individuals affected by hereditary syndromes associated with aberrant repair of DNA double-strand breaks points towards an important role of this pathway in lymphomagenesis. Single nucleotide polymorphisms (SNPs) that affect DNA repair mechanisms can increase the likelihood of pre-neoplastic lesions that may be relevant to lymphoma. To explore this further, we investigated the association of genetic variability in DNA double-strand break repair related genes with lymphoma risk using samples of the EpiLymph study, a European case-control study of lymphoma among adults conducted in between 1998 and 2004 in six European countries (Germany, Spain, France, Ireland, Italy, Czech Republic).

Material and methods: In total, 108 SNPs in 14 genes related to the DNA repair machinery were genotyped in 1481 cases and 1491 controls of the EpiLymph study using the Illumina GoldenGate Bead ArrayTM technology. Associations between SNPs and haplotypes and risk for Hodgkin lymphoma (HL), T-cell lymphoma, B-NHL and the most frequent B-NHL subtypes were estimated by calculating Odds Ratios (OR), the corresponding 95% confidence intervals (CI) and p-values using unconditional logistic regression, using SAS 9.2. Statistical interaction for the subsequent gene x gene and gene x environment interaction analysis was tested using the log-likelihood ratio test.

Results: Carriers of the mutant allele of the RAD54B SNP (rs10093542) presented a decreased risk for B-NHL with study-wise significance (ORAG/GG 0.55, 95%CI 0.40-0.75, p=0.0001), as well as for DLBCL (ORAG/GG 0.42, 95%CI 0.25-0.69, p=0.0006). The homozygous mutant genotype of the RAD52 SNP (rs11571475) conferred a 4-fold increased HL risk with study-wise significance (ORGG 4.41, 95%CI 1.89-10.28, p=0.0006). The increase in risk in association with the presence of rs11571475 G-alleles was seen only for ever smokers (p-trend = 0.0003), but not for never smokers (p-trend = 0.4). The risk for B-cell lymphoma was affected by gene x gene interaction between RAD54B or RAD54L variants and MRE11A polymorphisms.

Conclusion: Our results revealed associations between polymorphisms in selected DNA repair genes (RAD54B, RAD52, MRE11A) and risk for B-NHL and HL. Suggested gene x gene interactions between different members of the DNA repair machinery as well as the observed interaction with smoking status in driving HL risk, provide interesting candidates for replication efforts in independent study populations and/or InterLymph pooled analysis.