Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma Journal Article

Authors: Rendleman, J.; Antipin, Y.; Reva, B.; Adaniel, C.; Przybylo, J. A.; Dutra Clarke, A.; Hansen, N.; Heguy, A.; Huberman, K.; Borsu, L.; Paltiel, O.; Ben-Yehuda, D.; Brown, J. R.; Freedman, A. S.; Sander, C.; Zelenetz, A.; Klein, R. J.; Shao, Y.; Lacher, M.; Vijai, J.; Offit, K.; Kirchhoff, T.
Article Title: Genetic variation in DNA repair pathways and risk of non-Hodgkin's lymphoma
Abstract: Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13-1.43, p = 6.77610 -5), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34-0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL. © 2014 Rendleman et al.
Journal Title: PLoS ONE
Volume: 9
Issue: 7
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2014-07-10
Start Page: e101685
Language: English
DOI: 10.1371/journal.pone.0101685
PROVIDER: scopus
PMCID: PMC4092067
PUBMED: 25010664
Notes: Export Date: 1 August 2014 -- CODEN: POLNC -- Source: Scopus
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MSK Authors
  1. Adriana Heguy
    85 Heguy
  2. Kenneth Offit
    507 Offit
  3. Andrew D Zelenetz
    546 Zelenetz
  4. Boris A Reva
    36 Reva
  5. Robert J. Klein
    59 Klein
  6. Chris Sander
    196 Sander
  7. Vijai Joseph
    117 Joseph
  8. Yevgeniy Antipin
    19 Antipin
  9. Nichole Hansen
    9 Hansen
  10. Mortimer J Lacher
    3 Lacher