• Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Rockville, MD, USA.
• Lifestyles and Environments Unit, Finnish Institute of Health and Welfare, Kuopio, Finland.
• Biostatistics Branch, DCEG, NCI, Rockville, MD, USA.
• Metabolic Epidemiology Branch, DCEG, NCI, Rockville, MD, USA.
• Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), Rockville, MD, USA. Electronic address: purduem@mail.nih.gov.

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and B-cell non-Hodgkin lymphoma (B-NHL). To investigate whether associations exist at lower exposure levels, we conducted a nested case-control study investigating serum PFAS concentrations and B-NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations of five PFAS among 706 cases (age at diagnosis = 55-93 years, median 73 years) and 706 controls individually matched on age at blood draw, sex, self-reported race and ethnicity, study center, and year of blood collection (the median follow-up years = 10). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for PFAS concentrations in relation to B-NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with B-NHL for any of the five PFAS. In analyses of histologic subtypes, perfluorohexane sulfonate (PFHxS) was significantly associated with DLBCL in a model adjusting for all other PFAS (OR for highest vs. lowest quintile = 2.19, 95 % CI = 1.21, 3.95; P_trend = 0.02), but not in a model without mutual adjustment (OR = 1.37, 95 % CI = 0.82, 2.29; P_trend = 0.26). We also observed an inverse association between perfluorononanoate and DLBCL (mutually-adjusted OR = 0.83, 95 % CI = 0.69, 0.99 per doubling in concentration), although the association was null among participants with blood drawn prior to 1997 (OR_<1997 = 1.00, 95 % CI = 0.82, 1.21; OR_≥1997 = 0.65, 95 % CI = 0.53, 0.79; P_interaction = 0.0003). In conclusion, our findings from a prospective cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of B-NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation.