Non-hodgkin lymphoma and circulating markers of inflammation and adiposity in a nested case-control study: the multiethnic cohort.

Background: Because immune dysfunction is thought to underlie the development of non-Hodgkin lymphoma (NHL), obesity and chronic inflammation may be involved in its etiology. We examined the association of prediagnostic inflammatory markers and adipokines with NHL risk.

Methods: We conducted a nested case-control analysis (272 cases and 541 matched controls) within the Multiethnic Cohort. Luminex technology was used to measure a 10-plex panel of cytokines, ELISA assays for adipokines, and an autoanalyzer for C-reactive protein (CRP). ORs and 95% confidence intervals (CI) for tertiles of analytes were estimated by conditional logistic regression.

Results: After a median time of 2.7 years from phlebotomy to diagnosis, interleukin (IL)-10 was significantly related to NHL risk (ORT3 vs. T1 = 3.07; 95%CI, 2.02-4.66; Ptrend < 0.001). TNF-α and IL-8 showed borderline elevated risks, whereas IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, and CRP were not associated with NHL. Leptin but not adiponectin was related to NHL risk (ORT3 vs. T1 = 0.48; 95%CI, 0.30-0.76; Ptrend < 0.001). Adjustment for body mass index did not substantially affect the risk estimates. Stratification by subtype indicated significant associations with IL-10 and leptin for follicular but not for diffuse large B-cell lymphoma. Excluding cases diagnosed less than 1 year after phlebotomy attenuated all associations.

Conclusions: IL-10 was the only cytokine and leptin the only adipokine associated with NHL, but due to the short follow-up time, preclinical effects cannot be excluded.

Impact: Although markers of inflammation and adiposity may provide new insights into the etiology of NHL, they need to be assessed many years before clinical diagnosis.