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Elevated serum sCD23 and sCD30 up to two decades prior to diagnosis associated with increased risk of non-Hodgkin lymphoma

Leukemia volume 29, pages 1429–1431 (2015)Cite this article

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Conditions involving severe immune dysregulation are strong risk factors for non-Hodgkin lymphoma (NHL).1 However, it is unclear whether subclinical immunologic perturbations influence NHL risk. We and other investigators have recently reported NHL associations with elevated prediagnostic serum concentrations of the immune markers soluble CD23 (sCD23), sCD27, sCD30, B-cell-attracting chemokine-1 (BCA1), soluble tumor necrosis factor receptor-2 (sTNFR2) and soluble vascular endothelial growth factor receptor-2 (sVEGFR2).2, 3, 4, 5, 6, 7 Although these findings support a role for immunologic effects in lymphomagenesis, the relatively short duration of follow-up after phlebotomy in these studies (10–13 years) limits the ability to rule out reverse causation as an explanation, given the potential for developing lymphomas to express these markers or indirectly affect their expression. Investigations within cohorts with longer follow-up time are needed to clarify the temporal nature of these associations. To that end, we conducted a nested case–control study investigating the serum levels of these analytes and NHL diagnosed up to 23 years after phlebotomy within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a cohort with banked fasting serum from 29 133 male Finnish smokers.

The ATBC Study was approved by the institutional review boards of the National Cancer Institute and the National Public Health Institute of Finland; written informed consent was obtained from all the participants.8 We identified 272 first-primary NHL cases diagnosed 2+ years after phlebotomy through 2009 via the Finnish Cancer Registry. Fifty-three multiple myeloma cases were also selected but excluded from this report. We individually matched controls (N=325) to cases by baseline age (±2 years), phlebotomy date (±30 days) and the number of previous specimen thaws from among participants alive and cancer-free at case diagnosis. Serum concentrations of the analytes were measured by enzyme-linked immunosorbant assay (sCD23, sCD27, sCD30; Bender Medsystems, Burlingame, CA, USA) and Luminex-based assay (BCA1, sTNFR2, sVEGFR2; EMD Millipore, Billerica, MA, USA). For sCD23, a 1:2 dilution was performed for batches 3 onward to account for low serum volumes for many of the test samples; statistical analyses of this analyte were restricted to these batches. Sera from case–control pairs were assayed consecutively within batches along with blinded quality-control pool replicates (n=32). Measurements were highly reproducible, with coefficients of variation for log-transformed concentrations <5%.

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Acknowledgements

This work was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, NIH, Bethesda, MD, USA

    M P Purdue, Q Lan, A Hildesheim, S J Weinstein, J N Hofmann, D Albanes & N Rothman

  2. Ontario Institute for Cancer Research, Toronto, ON, Canada

    M P Purdue

  3. HPV Immunology Laboratory, Leidos Biomedical Incorporated, Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    T J Kemp & L A Pinto

  4. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    J Virtamo

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  1. M P Purdue
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Correspondence to M P Purdue.

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Purdue, M., Lan, Q., Kemp, T. et al. Elevated serum sCD23 and sCD30 up to two decades prior to diagnosis associated with increased risk of non-Hodgkin lymphoma. Leukemia 29, 1429–1431 (2015). https://doi.org/10.1038/leu.2015.2

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