Lymphoma-Associated Biomarkers Are Increased in Current Smokers in Twin Pairs Discordant for Smoking

SIMPLE SUMMARY: Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To help understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. We validated self-reported smoking history by measuring serum cotinine, a metabolite of nicotine, from previously collected frozen serum samples. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). We found that four immune response biomarkers were higher and one was lower among smoking compared to non-smoking twins. The strongest association was observed for CCL17/TARC, a biomarker elevated in Hodgkin lymphoma patients. Immune biomarker levels were similar in former smokers and non-smokers. Current smoking may increase levels of immune proteins that could partially explain the association between smoking and risk of certain lymphomas. ABSTRACT: Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of >3.08 ng/mL and ≤3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (P(trend) < 0.05). The strongest association was observed for CCL17/TARC (P(trend) = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas.