Abstract 5474: Prediagnostic cytokine levels and the risk of non-Hodgkin lymphoma in a nested case-control study: The Multiethnic Cohort

Abstract

Abstract Objective: Since immune dysfunction is thought to be the underlying basis for the development of Non-Hodgkin Lymphoma (NHL), obesity and a state of chronic inflammation may increase the risk of the disease. The objective of this analysis was to examine the association of prediagnostic inflammatory marker and adipokine levels in serum with NHL risk. Methods: We conducted a nested case-control analysis (272 cases and 578 controls) within the Multiethnic Cohort Study, which consists of Caucasians, Japanese Americans, Latinos, African Americans, and Native Hawaiians in California and Hawaii. Each case was matched to 2 controls by sex, year of birth, ethnicity, location (HI or CA), date and time of blood draw, and fasting hours before blood draw. A 10-plex panel of cytokines (TNF-α, IFN-γ, GM-CSF, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, and IL-10) was measured in prediagnostic blood samples by Luminex multiplex technology. ELISA assays were used for the adipokines, and CRP was assessed using a Cobas MiraPlus clinical chemistry analyzer. Tertiles of analytes were created and conditional logistic regression was applied to estimate the odds ratios (OR) and 95% confidence intervals (CI), with adjustment for age at blood draw, alcohol, smoking status, and body mass index (BMI). Results: The mean ages at blood draw were 70.0±7.4 and 70.3±7.6 years for cases and controls, respectively. The mean time from blood draw to diagnosis was 3.1±2.3 years with NHL cases comprised of the following lymphoma: 82 diffuse large B-cell, 51 small cell/chronic lymphocytic leukemia, 49 follicular, 15 T-cell, and 75 others. Of all cytokines, IL-10, IL-6, and IL-8 were positively associated with risk for NHL. The respective BMI-adjusted ORsT3v vs T1 were 3.1 (95%CI: 2.0-4.7; ptrend <0.0001), 1.3 (95%CI: 0.9-1.9; ptrend=0.09), and 1.5 (95%CI: 1.0-2.2; ptrend=0.11). No significant associations were observed for TNF-α, IFN-γ, GM-CSF, IL-1β, IL-2, IL-4, IL-5, and CRP. Leptin levels were inversely associated with NHL risk, with a stronger association after adjustment for BMI (ORT3v vs T1 = 0.3, 95%CI: 0.2-0.5; ptrend<0.001), but adiponectin was not related to risk. The lower risk associated with higher leptin levels was present in normal and in overweight/obese individuals. We did not observe any heterogeneity by sex or ethnicity for cytokines and adipokines. Conclusions: Contrary to expectation, higher IL-10 levels were associated with a higher NHL risk, and higher leptin levels were related to a lower NHL risk, even after adjustment for BMI. The limited sample size and the relatively short time between blood draw and diagnosis may have contributed to these findings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5474. doi:1538-7445.AM2012-5474