Plasma Cytokines and Future Risk of Non-Hodgkin Lymphoma (NHL): a Case-control Study Nested in the Italian European Prospective Investigation into Cancer and Nutrition

Background: Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general population.

Methods: Using bead-based immunoassays, plasma levels of 11 cytokines, 4 chemokines, and 1 adhesion molecules were measured in prediagnostic blood samples of 86 NHL cases and 86 matched controls (average time between blood collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for body mass index and alcohol consumption was used to analyze the association between individual plasma cytokine levels and the risk of developing NHL.

Results: In multivariate models, excluding cases diagnosed within 2 years after inclusion, we observed a significant association for interleukin 2 (IL2; P trend = 0.004), interferon (IFN)-gamma (P trend = 0.05), and intercellular adhesion molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a significant association with IL2 (P trend = 0.003), tumor necrosis factor-alpha (TNF-alpha; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association with IL5 (P trend = 0.07) and IFN-gamma (P trend = 0.08).

Conclusions: The results of this study suggest, in a prospective setting, a possible association between plasma levels of IL2, ICAM, IFN-gamma, and TNF-alpha with NHL risk and provide some evidence that risk of NHL might be related to a downregulation of T helper 1 cytokines.

Impact: Identification of subtle changes in immune response regulation quantified by plasma cytokine levels possibly provides new insights in the etiology of NHL.