Pre-diagnostic serum concentrations of free light chains and risk of non-Hodgkin lymphoma in a population-based prospective study.

Elevated serum free light chains (sFLC) indicate immune stimulation and have been associated with increased risk of AIDS-related non-Hodgkin lymphoma (NHL) and post-transplant lymphoproliferative disorder. This study examined 292 incident NHL cases and individually matched controls using pre-diagnostic samples from the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Higher κ (ptrend < 0.001) and λ (ptrend = 0.01) sFLCs were associated with increased overall NHL risk, particularly above the upper limit of normal (κ OR = 1.5, 95% CI = 0.9-2.6; λ OR = 4.7, 95% CI = 1.3-16.2). Elevated κ was linked to chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) risk (ptrend = 0.001), while elevated λ was associated with increased follicular lymphoma (FL) risk (ptrend = 0.02), with the latter showing consistent associations regardless of follow-up time. In CLL/SLL, polyclonal FLC elevations appeared >5 years before diagnosis, while monoclonal patterns emerged ≤5 years prior, supporting a progression from chronic immune stimulation to monoclonal B cell lymphocytosis (MBL).