Abstract 5073: Serum sCD23 and sCD30 associated with non-Hodgkin lymphoma risk as far as 15 to 23 years after blood collection

Background: We and other investigators have recently reported associations between elevated serum concentrations of selected immune markers and subsequent risk of non-Hodgkin lymphoma (NHL). While these findings support a role for subtle immunologic effects in lymphomagenesis, the relatively short length of follow-up after phlebotomy in these studies (10-13 years) limits the ability to rule out reverse causation as an explanation for these findings. To clarify the temporal nature of these associations, we conducted a nested case-control study investigating serum levels of six immune markers and NHL diagnosed up to 23 years after phlebotomy within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a cohort with banked fasting serum from 29,133 male Finnish smokers. Methods: We selected 272 first-primary NHL cases diagnosed 2+ years after phlebotomy, identified through linkage with the Finnish Cancer Registry, and 325 controls individually matched to cases on baseline age, phlebotomy date, and number of previous specimen thaws. Serum from these individuals were tested for soluble CD23 (sCD23), sCD27, sCD30, B cell attracting chemokine-1 (BCA-1), soluble tumor necrosis factor receptor-2 (sTNFR-2), and soluble vascular endothelial growth factor receptor-2. Odds ratios (OR) and 95% confidence intervals (CI) relating categories of analyte concentration to NHL risk were computed through conditional logistic regression with adjustment for cigarette pack-years. Polytomous regression models were also fit to compute ORs for the two most common NHL histologic subtypes, chronic lymphocytic leukemia (CLL) and diffuse large B cell lymphoma (DLBCL). Results: We observed NHL associations with elevated pre-diagnostic concentrations of the B cell activation markers sCD23 (highest analyte category vs. lowest: OR 2.4, 95% CI 1.5-3.8, Ptrend = 0.0005) and sCD30 (OR 3.3, 95% CI 1.9-5.5, Ptrend < 0.0001). The associations with sCD23 and sCD30 were apparent for cases diagnosed as far as 15-23 years after blood collection (OR 5.1, 95% CI 1.8-14.6, Ptrend = 0.002 and OR 3.7, 95% CI 1.5-9.3, Ptrend = 0.01 respectively). In subtype-specific analyses, both sCD23 and sCD30 were significantly associated with DLBCL, both overall and in later follow-up periods. sCD23 was significantly associated with CLL, particularly for earlier follow-up periods, while sCD30 was not. Associations with NHL were observed for sCD27, BCA-1, and sTNFR-2 but became weaker or null for cases dia