UCLA

Childhood cancer, defined as cancer diagnoses in children aged 0 to 19 years, is the second leading cause of death in children in the Unites States and Europe. The etiology of childhood cancer remains unclear. Established risk factors include genetic predispositions, high dose ionizing radiation, and prior chemotherapy. This dissertation examines three types of environmental exposures in relation to childhood cancer: 1) neonatal exposure to PFAS and the risk of retinoblastoma; 2) maternal residential proximity to oil and gas development during pregnancy and the risk of childhood cancer; and 3) parental occupational exposures to organic solvents and the risk of childhood cancer. The first study utilized 501 retinoblastoma cases and 899 controls born 1983-2011 from a population-based case-control study. We identified PFOS, PFOA, and PFNA feature intensities in neonatal DBS from California GDSP. Among all children, above-mean PFOS levels increased the risk of retinoblastoma overall (aOR: 1.29; 95% CI: 1.00, 1.67) and unilateral retinoblastoma (aOR: 1.42; 95% CI: 1.03,1.97). In children of Mexico-born mothers, above-mean PFOS levels increased the risk of retinoblastoma overall (aOR: 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92). In children of US-born mothers, the risk of unilateral retinoblastoma increased by 15% for each IQR increase in PFOS (95% CI: 0.99, 1.35) and by 71% (95% CI: 1.04, 2.90) for above-mean PFOS levels. PFOA increased the risk of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.06; 95% CI: 0.98, 1.16 per IQR increase) for children of US-born mothers. The second study utilized the same population-based case-control study in California with children born 1998-2016. We estimated exposure during pregnancy to any well (i.e., active or inactive) and inactive wells located within 1km and 3km of residences and assessed low and high exposures (categorized by median) within this proximity. The risk of medulloblastoma increased among children of mothers exposed to any well within 3km (≥1 well: adjusted Odds Ratio (aOR): 1.40; 95% confidence interval (CI): 1.08, 1.82; low, aOR = 1.27; 95% CI = 0.93, 1.74; high, aOR = 1.55; 95% CI = 1.14, 2.11). The risk of rhabdomyosarcoma consistently increased across the exposure levels of any well within 3km (≥1 well: aOR = 1.64; 95% CI = 1.28, 2.09; low, aOR = 1.69; 95% CI = 1.28, 2.23; high, aOR = 1.57; 95% CI = 1.16, 2.12). Similar associations were observed for teratoma with any well within 3km (≥1 well: aOR = 1.42; 95% CI = 0.99, 2.05; low, aOR = 1.35; 95% CI = 0.88, 2.07; high, aOR = 1.51; 95% CI = 0.98, 2.33). Overall, the results were consistent across the buffer sizes and no differences were found between any well and inactive wells. The third study utilized a linkage of four Danish data registries, including 10442 cases and 261050 controls born 1968-2013. Using JEMs, we identified and examined the role of parental occupational exposure to 3 hydrocarbon groups (i.e., aromatic, aliphatic/alicyclic, chlorinated hydrocarbons) and 4 individual hydrocarbons (i.e., toluene, DCM, TCE, 1,1,1-TCA) in two biologically relevant time periods: 1) 3 months preconception to birth for fathers; and 2) during pregnancy for mothers and the risk of childhood cancer in offspring. Paternal exposure to aromatic (high: aOR: 1.31; 95% CI: 0.95, 1.81) and chlorinated hydrocarbons (high: aOR: 1.82; 95% CI: 1.18, 2.82) increased the risk of glioma. The risk of AML was higher among fathers highly exposed to aliphatic/alicyclic hydrocarbons (high: aOR: 1.87; 95% CI: 1.24, 2.82). Paternal exposure to1,1,1-trichloroethane increased the risk of osteosarcoma (high: aOR: 2.29; 95% CI: 1.25, 4.18). The risk of medulloblastoma increased in offspring of mothers ever exposed to DCM (aOR: 1.69; 95% CI: 1.01, 2.84), TCE (aOR; 1.86; 95% CI: 1.12, 3.10), and toluene (aOR; 1.92; 95% CI: 1.07, 3.46). The risk of ALL increased in children of mothers ever exposed to aromatic hydrocarbons (aOR; 1.29; 95% CI: 1.01, 1.64), and 1,1,1-TCA (aOR; 1.30; 95% CI: 1.01, 1.69), while risk of NHL was associated with maternal exposure to chlorinated hydrocarbons (aOR; 1.94; 95% CI: 1.05, 3.57).