Early-life exposures to extreme weather-related factors and pediatric thyroid cancer risk - The goal of the proposed project is to evaluate early-life exposures to extreme weather-related factors and pediatric thyroid cancer risk. The incidence rate of pediatric thyroid cancer (ages 0-19 years) has been increasing in the United States, doubling from 2000 through 2019. Compared to adults, children tend to present at more advanced stages with larger tumor sizes, involvement of regional lymph nodes, and pulmonary metastasis. Moreover, children with thyroid cancer face a lifetime of surveillance, risk for second primary malignancies, disruptions of life milestones, and serious psychosocial outcomes. The vast majority of pediatric cases have unknown etiology. A limited but emerging literature among adults suggests that exposure to extreme temperatures (hot or cold) and air pollutants and may be linked to increased risk of thyroid cancer. Yet, the influence of these factors on pediatric cancer risk remains largely unstudied. We hypothesize that exposure to extreme temperature and air pollution are contributing to the rising incidence in pediatric thyroid cancer through perturbations of the thyroid endocrine system and function. We propose a large, nested case-control study within a statewide California birth cohort to examine the relationships between early-life exposures to ambient temperature, outdoor air pollution, and risk of pediatric thyroid cancer. Our study population includes 1,326 children born in California during 1982-2021 and diagnosed with first, primary thyroid cancer at the age of 0-19 years during 1988-2021 (i.e., cases), and 66,300 controls (50:1 match) matched to cases on birth year and sex. The proposed project will have an unprecedented sample size, covering cancer diagnoses over a 34-year span. Our study will utilize rich environmental geospatial data and employ innovative statistical and bioinformatics methods, including modeling multiple exposure windows. We will assess the relationship between early-life exposure to extreme ambient temperatures (heat, cold, heat waves, cold waves) and pediatric thyroid cancer risk and examine whether there are different patterns by cancer subtype, age, timing of exposure, or other factors (Aim 1). We will also assess potential associations between early-life exposure to ambient air pollution (fine particulate matter, nitrogen dioxide) and pediatric thyroid cancer risk and examine whether there are different patterns by cancer subtype, age, exposure timing, or other factors (Aim 2). We will also evaluate possible interaction effects between temperature and air pollution. Given the rapid increase in pediatric thyroid cancer incidence and the widespread exposure to extreme weather and air pollution, this innovative and timely study will help to elucidate the obscure etiology of an understudied cancer, clarify the impact of extreme weather and related factors on childhood carcinogenesis, and inform strategies to mitigate environmental exposures and risks.
