Case-Cohort Study of the Association between PFAS and Selected Cancers among Participants in the American Cancer Society's Cancer Prevention Study II LifeLink Cohort

Background: Previous epidemiological studies found associations between exposure to per- and polyfluoroalkyl substances (PFAS) and some cancer types. Many studies considered highly exposed populations, so relevance to less-exposed populations can be uncertain. Additionally, many studies considered only cancer site, not histology.

Objectives: We conducted a case-cohort study within the American Cancer Society's prospective Cancer Prevention Study II (CPS-II) LifeLink cohort to examine associations between PFAS exposure and risk of selected cancers, considering histologic subtypes.

Methods: Serum specimens were collected from cohort participants during the period 1998-2001. This study included a subcohort (500 men, 499 women) randomly selected from participants without prior cancer diagnoses at serum collection, and all participants with incident (after serum collection) first cancers of the breast (females only, $n=786$), bladder ($n=401$), kidney ($n=158$), pancreas ($n=172$), prostate (males only, $n=\mathrm{1,610}$) or hematologic system ($n=635$). PFAS concentrations [perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] were measured in stored serum. We assessed associations between PFAS concentrations and incident cancers, by site and histologic subtype, using multivariable Cox proportional hazards models stratified by sex and controlling for age and year at blood draw, education, race/ethnicity, smoking, and alcohol use.

Results: Serum PFOA concentrations were positively associated with renal cell carcinoma of the kidney among women [hazard ratio (HR) and 95% confidence interval (CI) per PFOA doubling: 1.54 (95% CI: 1.05, 2.26)] but not men. Among men, we observed a positive association between PFHxS concentrations and chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL, HR and 95% CI per PFHxS doubling: 1.34 (95% CI: 1.02, 1.75)]. We observed some heterogeneity of associations by histologic subtype within sites.

Discussion: This study supports the previously observed association between PFOA and renal cell carcinoma among women and suggests an association between PFHxS and CLL/SLL among men. Consideration of histologic subtypes might be important in future studies of PFAS-cancer associations. https://doi.org/10.1289/EHP13174.