Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies Journal Article

Authors: Vijai, J.; Kirchhoff, T.; Schrader, K. A.; Brown, J.; Dutra Clarke, A. V.; Manschreck, C.; Hansen, N.; Rau-Murthy, R.; Sarrel, K.; Przybylo, J.; Shah, S.; Cheguri, S.; Stadler, Z.; Zhang, L.; Paltiel, O.; Ben-Yehuda, D.; Viale, A.; Portlock, C.; Straus, D.; Lipkin, S. M.; Lacher, M.; Robson, M.; Klein, R. J.; Zelenetz, A.; Offit, K.
Article Title: Susceptibility Loci Associated with Specific and Shared Subtypes of Lymphoid Malignancies
Abstract: The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (PLYM = 3.89×10-8, OR = 1.29) and rs948562 (PLYM = 5.85×10-7, OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, PNHL = 5.72×10-7) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (PFL = 2.69×10-12, OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy. © 2013 Vijai et al.
Journal Title: PLoS Genetics
Volume: 9
Issue: 1
ISSN: 1553-7390
Publisher: Public Library of Science  
Date Published: 2013-01-01
Start Page: e1003220
Language: English
DOI: 10.1371/journal.pgen.1003220
PROVIDER: scopus
PMCID: PMC3547842
PUBMED: 23349640
Notes: --- - "Export Date: 1 March 2013" - "Source: Scopus"
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MSK Authors
  1. Kenneth Offit
    507 Offit
  2. Carol Portlock
    178 Portlock
  3. Mark E Robson
    365 Robson
  4. Liying Zhang
    88 Zhang
  5. Zsofia Kinga Stadler
    144 Stadler
  6. Andrew D Zelenetz
    546 Zelenetz
  7. Agnes Viale
    205 Viale
  8. Robert J. Klein
    59 Klein
  9. Vijai Joseph
    117 Joseph
  10. Sohela Shah
    15 Shah
  11. David J Straus
    205 Straus
  12. Nichole Hansen
    9 Hansen
  13. Kara Lindsay Sarrel
    7 Sarrel
  14. Mortimer J Lacher
    3 Lacher