PROJECT SUMMARY/ABSTRACT
Per- and polyfluoroalkyl substances (PFAS) have been used in many manufacturing and commercial products
in recent decades, resulting in widespread and persistent contamination despite the phasing out of early
compounds such as PFOS and PFOA. Routes of PFAS exposure to humans vary by age; while exposures in
infants and children are commonly from breastfeeding and ingestion of settled dust, adolescents and adults are
primarily exposed through food and water. PFAS have been associated with several adverse health outcomes,
including cancer in adults. Despite several reports of childhood cancer clusters in PFAS-contaminated areas,
and potentially higher body burdens in children compared to adults, no studies have systematically assessed
cancer risk in children, due, in part to the relative rarity of childhood cancer. We propose to conduct the first
study of PFAS and cancer in children, by integrating the expertise of investigators from four institutions, forming
a transdisciplinary virtual consortium with expertise in pediatric and cancer epidemiology, and environmental
engineering and health sciences. Using innovative methodology, this virtual consortium will characterize PFAS
from the most relevant routes of exposure by examining PFAS in drinking water (Aim 1), newborn and pregnancy
blood samples (Aim 2), and household dust (Aim 3) during vulnerable exposure windows from pregnancy through
early childhood, and subsequent risk of developing childhood cancer. We will focus on cancers that have been
reported previously in communities and groups known to have high exposures to PFAS, such as leukemia,
rhabdomyosarcoma, lymphoma, and cancers of the brain, central nervous system, kidney, testis, and thyroid.
We will leverage two existing California childhood cancer studies with complementary designs offering large
number of childhood cancer cases and controls with residential information, and with access to blood and dust
samples for subsets. PFAS water exposure assessment, we will use a Bayesian pharmacokinetic calibration
approach that combines measured drinking water concentrations with measured serum biomarkers to provide
improved exposure estimates. We will also combine targeted and non-targeted mass spectrometric strategies to
measure PFAS in blood and dust samples. There will be synergy between the three research aims by
overlapping study participants (Aims 1 and 2), coordinating laboratory analyses (Aims 2 and 3) and statistical
analyses (Aims 1, 2, 3), and by paying special attention to leukemia--the most common childhood cancer (Aims
1, 2, 3). The ViCTER Consortium will be supported by an Administrative and Scientific Oversight Core to
coordinate and integrate resources and activities of the three research aims. With our unique resources, novel
methods, and complementary expertise, this proposal responds to the urgent need of assessing population
cancer risk to children related to PFAS.