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Human leukocyte antigen (HLA) A1-B8-DR3 (8.1) haplotype, tumor necrosis factor (TNF) G-308A, and risk of non-Hodgkin lymphoma

Leukemia volume 24, pages 1055–1058 (2010)Cite this article

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Large-scale consortial efforts now provide convincing evidence that the pro-inflammatory cytokine tumor necrosis factor (TNF) promoter polymorphism (TNF G-308A), which is thought to increase TNF-α protein expression resulting in inflammation, is associated with increased risk of non-Hodgkin lymphoma (NHL) and specifically with the NHL subtype, diffuse large B-cell lymphoma (DLBCL) among Caucasians.1 The largest effort to date from the International Lymphoma Epidemiology Consortium (InterLymph) comprising 7999 incidence NHL cases and 8452 controls report that TNF-308A carriers have a 1.25-fold (per allele) increased risk for DLBCL and a 1.35-fold increased risk for marginal zone lymphoma.2

A limitation to the published association studies, however, is the inability to delineate the association between TNF and NHL from human leukocyte antigen (HLA) alleles that are known to be in linkage disequilibrium. TNF is located on chromosome 6p21.3 among the Class III genes of the major histocompatibility complex, 250 kb centromeric to the HLA-B locus and 850 kb telomeric to the Class II HLA-DR locus. It is well documented that Caucasian populations carry the 8.1 ancestral haplotype (AH) that includes the TNF-308A allele (HLA-A1-B8-TNF-308A-DR3-DQ2).3 Notably, the 8.1 AH is implicated in the risk of numerous autoimmune conditions, including those associated with NHL (for example, systemic lupus erythematosus and Sjogren's syndrome).3, 4, 5 It remains unknown, however, whether the association reported for TNF-308A is due to or independent from HLA alleles and/or haplotypes.

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Acknowledgements

We thank Peter Hui of the Information Management Services Inc. for programming support. We also gratefully acknowledge the contributions of the staff and scientists at the SEER centers of Iowa, Los Angeles, Detroit and Seattle for the conduct of the study's field effort. We especially acknowledge the contributions of study site principle investigators Richard Severson (Detroit) and Leslie Bernstein (Los Angeles), without whom the study would not have been possible. The NCI-SEER study was supported by the Intramural Research Program of the NIH (NCI), and by Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105.

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Authors and Affiliations

  1. Basic Research Program, SAIC-Frederick Inc. Laboratory of Genomic Diversity, NCI-Frederick, Frederick, MD, USA

    A M Abdou, X Gao, M P Martin & M Carrington

  2. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    W Cozen

  3. Mayo Clinic, College of Medicine, Rochester, MN, USA

    J R Cerhan

  4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA

    N Rothman, P Hartge & S S Wang

  5. Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA

    S Davis

  6. Department of Family Medicine and Public Health Sciences, Wayne State University and the Karmanos Cancer Institute, Detroit, MI, USA

    M Schenk

  7. Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, NIH, DHHS, Gaithersburg, MD, USA

    S J Chanock

  8. Division of Etiology, Department of Population Sciences, Beckman Research Institute and the City of Hope, Duarte, CA, USA

    S S Wang

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  1. A M Abdou
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Correspondence to S S Wang.

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Abdou, A., Gao, X., Cozen, W. et al. Human leukocyte antigen (HLA) A1-B8-DR3 (8.1) haplotype, tumor necrosis factor (TNF) G-308A, and risk of non-Hodgkin lymphoma. Leukemia 24, 1055–1058 (2010). https://doi.org/10.1038/leu.2010.17

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