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Keywords:

  • Lyme disease;
  • Borrelia burgdorferi;
  • malignancy;
  • cancer

To the Editor,

Based on data extracted from a large Swedish cancer registry, Chang et al. arrive at the conclusion that infection with Borrelia burgdorferi, the spirochetal agent of Lyme disease, is not associated with an increased risk of malignancy.1 Their study has two major flaws that make the results impossible to interpret.

First, the authors relied on a positive enzyme-linked immunosorbent assay (ELISA) to make a diagnosis of B. burgdorferi infection in study subjects. It is known that the ELISA tests used in Europe and Scandinavia are only positive in 34–59% (mean, 46%) of patients infected with the Lyme disease spirochete,2 and the commercial ELISA test employed in the study has been plagued with false-negative IgG results.3 Thus the actual number of B. burgdorferi-infected patients may have been more than double the number recorded in the study, and the association with malignancy may have been significantly underestimated because of the insensitive ELISA test results. Furthermore, other tickborne diseases such as rickettsiosis have been associated with lymphoid malignancy,4 and the study failed to identify tickborne coinfections that may accompany B. burgdorferi and increase the malignancy risk.

Second, the authors claim that “cervical, lung and prostate cancer were significantly associated with Borrelia” based on the hazard ratios for various malignancies listed in Table 1. However, closer scrutiny reveals that the risks of cervical and lung cancer were in fact decreased in patients with B. burgdorferi infection, with hazard ratios of 0.56 and 0.68, respectively. In contrast, hazard ratios for prostate cancer (1.24), bladder cancer (1.26), chronic lymphocytic leukemia (1.39) and myeloproliferative neoplasm (1.40) were increased in patients infected with the Lyme spirochete, but only the association with prostate cancer reached statistical significance because of small numbers in the other malignancy subsets. Thus, there appears to be a heterogeneous effect of B. burgdorferi infection on the risk of various malignancies, and this effect is difficult to interpret based on the limited retrospective data presented here.

In summary, lack of reliable testing for B. burgdorferi infection, failure to consider tickborne coinfections, and variable spirochetal effects on the risk of different malignancies make the data of Chang et al. impossible to interpret. With better testing for spirochetal infection and better understanding of B. burgdorferi pathophysiology, more meaningful data about the risk of malignancy associated with this elusive spirochete should be forthcoming. In particular, the interplay between different strains of B. burgdorferi, chronic immune stimulation induced by tickborne pathogens, and lymphoid malignancies arising in privileged sites merits further study.4–7

References

  1. Top of page
  • 1
    Chang CM, Landgren O, Koshiol J, Björkholm M, Löve TJ, Kristinsson SY. Borrelia and subsequent risk of solid tumors and hematologic malignancies in Sweden. Int J Cancer, in press.
  • 2
    Ang CW, Notermans DW, Hommes M, Simoons-Smit AM, Herremans T. Large differences between test strategies for the detection of anti-Borrelia antibodies are revealed by comparing eight ELISAs and five immunoblots. Eur J Clin Microbiol Infect Dis 2011; 30: 102732.
  • 3
    Petersen E, Tolstrup M, Capuano F, Ellermann-Eriksen S. Population-based study of diagnostic assays for Borrelia infection: comparison of purified flagella antigen assay (IDEIA, Dako Cytomation) and recombinant antigen assay (Liaison, DiaSorin). BMC Clin Pathol 2008; 8: 4.
  • 4
    Koshiol J, Gridley G, Engels EA, McMaster ML, Landgren O. Chronic immune stimulation and subsequent Waldenstrom macroglobulinemia. Arch Intern Med 2008; 168: 19039.
  • 5
    Cerroni L, Höfler G, Bäck B, Wolf P, Maier G, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at sites typical for Borrelia burgdorferi infection. J Cutan Pathol 2002; 29: 1427.
  • 6
    Dalle S, Thomas L, Balme B, Dumontet C, Thieblemont C. Primary cutaneous marginal zone lymphoma. Crit Rev Oncol Hematol 2010; 74: 15662.
  • 7
    Kash N, Fink-Puches R, Cerroni L. Cutaneous manifestations of B-cell chronic lymphocytic leukemia associated with Borrelia burgdorferi infection showing a marginal zone B-cell lymphoma-like infiltrate. Am J Dermatopathol 2011; 33: 7125.

Raphael B. Stricker*, Lorraine Johnson*, * International Lyme and Associated Diseases Society, Bethesda, MD.