Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype

Int J Cancer. 2014 Aug 15;135(4):913-22. doi: 10.1002/ijc.28724. Epub 2014 Feb 3.


Specific associations for lymphoma in the general population suggest that chronic immune dysfunction/dysregulation may be associated with the development of B-cell non-Hodgkin lymphoma (NHL). Furthermore, polymorphisms in several cytokine genes have been associated with increased lymphoma risk, most consistently with genes for TNF and IL10. To evaluate the hypothesis that prediagnostic circulating cytokine levels would be associated with increased B-cell lymphoma risk, we conducted a nested case-control study within the Women's Health Initiative Observational Study cohort involving 491 B-cell NHL cases and 491 controls. Levels of eleven cytokines, including IL1β, IL2, IL4, IL5, IL6, IL10, IL12, IL13, TNF, IFNγ and GM-CSF, were measured using a Luminex suspension bead-based multiplexed array in prediagnostic serum samples collected a median of 6 years prior to the lymphoma diagnosis. We observed a modestly increased risk of all B-cell NHL in women with increased levels of the cytokines TNF and IL10 (OR1.22, CI 1.07-1.38 and OR 1.09, CI 1.04-1.15, respectively, per doubling in the serum cytokine concentration) and this association showed some variation according to histologic subtype. The increased risk was strongest for those neoplasms diagnosed in close proximity to the blood draw for some histologic subtypes but not others, suggesting a component of reverse causation. Further study will be required to better understand how genetic polymorphisms in TNF and IL10 genes may interact with circulating cytokine levels and states of chronic immune dysfunction/stimulation to contribute to the risk of B-cell NHL.

Keywords: cohort studies; cytokines; epidemiology; non-Hodgkin lymphoma.

Publication types

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

MeSH terms

  • Aged
  • Alleles
  • Biomarkers, Tumor / blood
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immune System
  • Inflammation
  • Interleukin-10 / blood
  • Lymphoma, B-Cell / blood*
  • Lymphoma, B-Cell / diagnosis
  • Lymphoma, Non-Hodgkin / blood*
  • Lymphoma, Non-Hodgkin / diagnosis
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Genetic
  • Postmenopause
  • Risk Factors
  • Tumor Necrosis Factor-alpha / blood


  • Biomarkers, Tumor
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10