Circulating sCD27 and sCD30 in pre-diagnostic samples collected fifteen years apart and future non-Hodgkin lymphoma risk

Elevated serum sCD27 and sCD30 from a single banked sample have been associated with future non-Hodgkin lymphoma risk (NHL); however, the etiologic relevance of this finding is unclear. To address this question, we conducted a case–control study (235 cases, 235 controls) nested within the CLUE-I and CLUE-II cohorts, which enrolled participants in 1974 and 1989 respectively in Washington County, Maryland. Our study features a subset of 102 cases and 102 controls with two banked pre-diagnostic samples each, collected 15 years apart. In analyses involving an individual sample per subject, both sCD27 and sCD30 were associated with NHL diagnosed up to 20 years later. In analyses involving repeated samples, cases were significantly more likely than controls to have higher analyte levels in the CLUE-II vs. CLUE-I sample for sCD27 (p = 0.006) but not sCD30 (p = 0.16). In joint analyses of dichotomized analyte levels in both samples, the strongest NHL association observed for sCD27 was for having below-median levels in CLUE-I and above-median levels in CLUE-II [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.4–9.2 vs. below-median levels in both). In joint analyses for sCD30, the strongest NHL association was observed for having above-median levels in both samples (OR 1.7, 95% CI 0.8–3.7), particularly for cases diagnosed >10 years after the CLUE-II sample (OR 2.4, 95% CI 0.9–6.7). Our findings suggest that sCD27 is a disease marker for NHL and add to the weight of evidence that elevated circulating sCD30 is a marker of increased NHL susceptibility.