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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4348-4354. Prepublished online as a Blood First Edition Paper on February 20, 2008; DOI 10.1182/blood-2007-09-112144. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-09-112144v1 111/8/4348    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Skibola, C. F Articles by Holly, E. A. Search for Related Content PubMed PubMed Citation Articles by Skibola, C. F Articles by Holly, E. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 11, 2007 Accepted February 13, 2008 A functional TNFRSF5 gene variant is associated with risk of lymphoma Christine F Skibola*, Alexandra Nieters, Paige M Bracci, John D Curry, Luz Agana, Danica R. Skibola, Alan Hubbard, Nikolaus Becker, Martyn T Smith, and Elizabeth A. Holly Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, United States Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States * Corresponding author; email: chrisfs{at}berkeley.edu. CD40 and its ligand, CD154, are major co-stimulatory molecules whose interactions are important in humoral and cellular immunity. We hypothesized that single nucleotide polymorphisms (SNPs) in TNFRSF5 and TNFSF5 encoding the CD40 and CD154 proteins, respectively, influence lymphoma risk, particularly a functional TNFRSF5 SNP (-1C>T, rs1883832) associated with reduced B-cell CD40 expression. TNFRSF5 and TNFSF5 SNPs were examined in a population-based case-control study of non-Hodgkin lymphoma (NHL) (376 cases/801 controls with DNA) and compelling findings were followed up in two independent populations. Pooled analyses of all three case-control studies (total N=1,776 NHL cases, N=2,482 controls) revealed an increased risk of follicular lymphoma (FL) associated with the TNFRSF5 -1TT genotype [odds ratio (OR)=1.6, 95% confidence interval (CI)=1.1-2.4]. Also, among women, an inverse association was found between the variant A allele for a TNFSF5 6809G>A SNP and FL risk (OR=.61, 95%CI=.36-.98). In genotype-phenotype studies, significantly reduced circulating soluble CD40 was observed in TNFRSF5 -1TT compared to -1CC carriers. Further, dendritic cells from those with -1TT versus -1CC genotypes exhibited lower CD40 cell surface expression. These results suggest that the TNFRSF5 -1C>T polymorphism may increase FL susceptibility through mechanisms that hinder cellular immune responses. Further studies are needed to explore these findings. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Ueffing, K. K. Singh, A. Christians, C. Thorns, A. C. Feller, F. Nagl, F. Fend, S. Heikaus, A. Marx, R. B. Zotz, et al. A single nucleotide polymorphism determines protein isoform production of the human c-FLIP protein Blood, July 16, 2009; 114(3): 572 - 579. [Abstract] [Full Text] [PDF] J. R. Cerhan, W. Liu-Mares, Z. S. Fredericksen, A. J. Novak, J. M. Cunningham, N. E. Kay, A. Dogan, M. Liebow, A. H. Wang, T. G. Call, et al. Genetic Variation in Tumor Necrosis Factor and the Nuclear Factor-{kappa}B Canonical Pathway and Risk of Non-Hodgkin's Lymphoma Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 3161 - 3169. [Abstract] [Full Text] [PDF]

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