Using targeted and non-targeted approaches to examine per- and polyfluoroalkyl substances (PFAS) exposure and glioma risk in young children - PROJECT SUMMARY In the United States (US), glioma accounts for 53% of tumors in the brain and central nervous system among children (0-14 years), causing more deaths than any other types of childhood cancer. The incidence of glioma is higher in younger children (0-5 years) than in older children (6-14 years), and it has been increasing in the US despite a decrease in overall cancer incidence during 2000-2018. The brain undergoes the fastest development during pregnancy and is susceptible to environmental exposures that may impact cancer risk, either on their own or jointly with genetic factors. The objective of this study is to investigate the etiology of glioma in young children, with a focus on prenatal exposure to per- and poly-fluoroalkyl substances (PFAS), while accounting for other putative risk factors for glioma, including genetic susceptibility. PFAS are a family of more than 10,000 fluorinated compounds. These chemicals are widely present and extremely persistent in clothing, furnishings, paper products, food packing, and kitchenware. There is strong evidence that PFAS can induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. As PFAS are known to cross the placenta during pregnancy and blood brain barriers and have been demonstrated to be neurotoxic, it is biologically plausible that prenatal PFAS exposure can interfere with multiple maternal-fetal systems at critical time windows and impact brain development. PFAS have been detected in surgically resected glioma tissue samples. In the proposed study, we will select 350 cases who were diagnosed with astrocytoma (the most common subtype of glioma in young children) in California at the age of 0-5 years from a population- based statewide linkage of birth records and cancer registry data, as well as 350 cancer-free controls from the same linkage, forming a nested case-control study within the California birth cohort. Using state-of-the-art technology to measure PFAS in the archived newborn blood specimens, we will pursue two aims: (1) conduct a targeted analysis of 13 PFAS and examine whether prenatal exposure to these legacy and alternative PFAS is associated with the risk of glioma in young children; and (2) conduct a non-targeted analysis to identify novel, previously unknown or unexpected PFAS and evaluate whether prenatal exposure to these PFAS is associated with glioma risk in young children. This study is distinguished by its rigorous study design, innovative focus on prenatal PFAS exposure using a unique resource from the California Biobank Program, application of novel exposure methods to comprehensive characterize PFAS beyond the several compounds that have been traditionally assessed, and the ability to account for other putative environmental and genetic risk factors. Responding to the urgent need to assess cancer risk related to PFAS, which are largely unregulated, our study will not only help elucidate the etiology of glioma in children but may also have policy implications.
