Markers of B-cell activation in relation to risk of non-Hodgkin lymphoma

Cancer Res. 2012 Sep 15;72(18):4733-43. doi: 10.1158/0008-5472.CAN-12-1639. Epub 2012 Jul 30.


B-cell activation biomarkers have been associated with increased risk of non-Hodgkin lymphoma (NHL) in HIV-infected populations. However, whether a similar association may exist in general populations has not been established. We conducted a case-control study within the Women's Health Initiative Observational Study cohort to measure the B-cell activation biomarkers sCD23, sCD27, sCD30, sCD44, and CXCL13 in serum samples collected an average of 6 years before NHL diagnosis in 491 cases and 491 controls. Using logistic regression to estimate odds ratios, we observed strong associations between NHL and markers for all B-cell NHL and for major subtypes. Women with marker levels in the highest-versus-lowest quartile categories of CD23, CD27, CD30, or CXCL13 were at 2.8- to 5.5-fold increased risk of B-NHL. In addition, there were significant trends of risk with increasing levels of these markers present. Associations were strongest for cases with shortest lag times between blood draw and diagnosis (<3 years). However, there were also significant associations for cases with the longest prediagnostic lag (9 to 13 years). Taken together, our findings indicate a prominent role for B-cell activation among postmenopausal women in the etiology of B-cell NHL and/or in processes reflective of early disease development as early as 9 years before diagnosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocytes / immunology*
  • Biomarkers, Tumor / immunology*
  • Case-Control Studies
  • Female
  • Humans
  • Lymphocyte Activation / immunology*
  • Lymphoma, Non-Hodgkin / immunology*
  • Middle Aged
  • Risk Factors


  • Biomarkers, Tumor