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Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma

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Abstract

Background

Tumor necrosis factor (TNF) and interleukin 10 (IL10) are promising candidate susceptibility genes for non-Hodgkin lymphoma (NHL). Chromosomal translocation breakpoint genes are of interest, given their documented involvement in lymphoma progression.

Methods

We analyzed 11 polymorphisms in BCL2, CCND1, MYC, TNF, and IL10 in a large, population-based, Danish-Swedish case–control study including 2,449 NHL cases and 1,980 controls. Relative risk of NHL was computed as odds ratios (OR).

Results

There was no clear evidence of associations between variants in BCL2, CCND1, and MYC and risk of NHL overall or subtypes. TNF rs1800629 was associated with risk of NHL (OR 1.53, 95% confidence interval, CI, 1.06–2.19 for minor allele homozygosity), T-cell lymphoma (OR 2.54, CI 1.27–5.09) and mantle cell lymphoma (OR 2.84, CI 1.38–5.87). IL10 rs1800890 was associated with risk of diffuse large B-cell lymphoma (OR 1.41, CI 1.08–1.85 for minor allele homozygosity) and mantle cell lymphoma (OR 1.77, CI 1.04–3.00). We did not replicate a previously reported interaction with autoimmunity.

Conclusions

We found no support for a role of the studied variants in BCL2, CCND1, or MYC in risk of NHL or subtypes, but we provide further evidence of putative susceptibility loci in TNF and IL10 for specific NHL subtypes.

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Acknowledgments

The study was funded by the Danish Medical Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Research Council.

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Authors and Affiliations

  1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, 171 77, Stockholm, Sweden

    Pia Fernberg, Sandra Eloranta & Keith Humphreys

  2. Northern California Cancer Center, Fremont, CA, USA

    Ellen T. Chang

  3. Department of Biosciences at Novum, Clinical Research Centre, Karolinska Institutet, Stockholm, Sweden

    Kristina Duvefelt

  4. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    Henrik Hjalgrim & Mads Melbye

  5. Molecular Genetics Laboratory, Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark

    Karina Meden Sørensen

  6. Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden

    Anna Porwit

  7. Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital, Stockholm, Sweden

    Karin Ekström Smedby

  8. Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA

    Ellen T. Chang

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  1. Pia Fernberg
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Correspondence to Pia Fernberg.

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Fernberg, P., Chang, E.T., Duvefelt, K. et al. Genetic variation in chromosomal translocation breakpoint and immune function genes and risk of non-Hodgkin lymphoma. Cancer Causes Control 21, 759–769 (2010). https://doi.org/10.1007/s10552-010-9504-y

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  • DOI: https://doi.org/10.1007/s10552-010-9504-y

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