Domestic radon exposure and childhood cancer risk by site and sex in 727 counties in the United States, 2001–2018 (original) (raw)

Elsevier

Science of The Total Environment

Highlights

Abstract

Background

Childhood cancer has few established risk factors and environmental influences are underexplored. This ecologic study investigated the association between domestic radon exposure and childhood cancer risk in a large sample of United States (U.S.) counties.

Methods

Monthly ZIP code-level basement radon estimates from a geographic machine learning model were aggregated annually to counties, analyzed as continuous and dichotomized (cut point: 74 Bq/cubic meter (Bq/m3) or 2.0 picocuries/L (pCi/L)) versions, and lagged by one year. Annual county-level counts of sex- and site-specific (all, leukemia, brain and central nervous system [CNS], and other sites) incident cancer diagnoses among those 0–19 years from 2001 to 2018 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database. Sex- and site-specific counts were modeled as zero-inflated Poisson distributions in a Bayesian spatiotemporal framework and sequentially adjusted for random and fixed confounder effects.

Results

In 727 counties across 14 states, the average population aged 0–19 years was 41,599 people at baseline. Results from fully adjusted spatiotemporal statistical models indicated 1.05 (95% credible interval, CrI: 1.00, 1.09) times higher relative risks (RRs) of leukemia among both sexes and a RR of 1.06 (95%CrI: 1.00, 1.12) in males from a 50 Bq/m3 (1.35 pCi/L) increase in radon concentration the year prior. For radon exposures ≥74 Bq/m3 (2.00 pCi/L) the year prior, RRs were 1.08 (95%CrI: 1.02, 1.15) for both sexes and 1.12 (95%CrI: 1.04, 1.22) for females. No associations were found with other cancer sites or sexes from prior year radon exposures.

Conclusions

County-level childhood leukemia risk in both sexes were associated with average radon levels below U.S. Environmental Protection Agency guidelines recommending mitigation (148 Bq/m3 or 4.00 pCi/L). These findings warrant further investigation using population-based and individual-level study designs.

Introduction

The causes of many childhood cancers remain poorly understood, and their rarity poses a challenge to studying etiologies. Moreover, childhood cancer rates are rising in United States (U.S.) (National Cancer Institute, 2022). The most common childhood cancers in the U.S. are leukemias (49.6 cases/100,000 children), brain and central nervous system (CNS) cancers (31.8/100,000), lymphomas (31.2/100,000), and epithelial neoplasms and melanomas (24.9/100,000) (National Cancer Institute, 2024a). Genetic factors explain only a small proportion of childhood cancers; and, though ionizing radiation from clinical diagnostic and treatment equipment has been a hypothesized cause, results from previous research have not been definitive (Roman et al., 2017).

Domestic radon-222 gas decay (radon hereafter), measured as the count of disintegrations per cubic meter (Becquerels/cubic meter, Bq/m3) per second with 37 Bq/m3 and equivalent to one picocurie per liter (pCi/L), was classified as a cause of lung cancer in humans (i.e. Group 1) in 1988 by IARC (International Agency for Research on Cancer, 2018). However, evidence for a role of radon decay products (alternatively, “progeny” or “daughters”) in other, non-lung cancers has been scarce and mixed in both adults and children (Bräuner et al., 2013; López-Abente et al., 2018; Moon and Yoo, 2021; Raaschou-Nielsen et al., 2008; Ruano-Ravina et al., 2017; Teras et al., 2016; Toti et al., 2005; Hauri et al., 2013; Del Risco et al., 2014; Henshaw et al., 1990). The mechanism for non-lung cancers is not well known, though approximately 90% of radon decay products have been shown to attach to aerosols and particulate matter (PM) (Porstendörfer, 1994), which can then emit highly toxic alpha particle radiation (Kang et al., 2020; Seiler and Wiemels, 2012). Via translocation within the body after inhalation or ingestion of radioactive PM or as a result of additional carcinogenic processes, internal bodily tissues other than lung tissues are exposed to toxic radiation (Vieira et al., 2020). Radiation doses to various bodily tissues from exposure to decay of radon have been shown to be higher in infants compared to adults (Kendall and Smith, 2005). The U.S. Environmental Protection Agency (EPA) states that no known level of radon is safe, and that homeowners should consider mitigation when indoor levels exceed 2.00 pCi/L (74 Bq/m3) and mitigation is recommended when levels are equal to or exceed 4.00 pCi/L (148 Bq/m3) (U.S. Environmental Protection Agency, 2019). More research on potential causes of childhood cancers are needed to clarify risk factors and better support U.S. EPA decision and policy-making.

The relationship between radon exposure and childhood cancer has been investigated in only a few studies; though a variety of designs have been used, evidence was mixed. Recent ecologic studies outside the U.S. have not found strong evidence to support a link between radon and childhood cancer (Demoury et al., 2017; Berlivet et al., 2020; Chen and Xie, 2019), though a 2006 study in France did find an association with acute myeloid leukemia (AML) (Evrard et al., 2006). Cohort studies in the greater Oslo region of Norway and Switzerland did not find associations between radon and childhood cancer (Hauri et al., 2013); however, there was evidence of possibly elevated risk of childhood CNS tumors from radon exposure in Norway (Del Risco et al., 2014). While case-control studies in the United Kingdom and Finland did not find links between radon and childhood cancers (Kendall et al., 2013; Nikkilä et al., 2020), a Danish case-control study found a positive association between radon and acute lymphoblastic leukemia (ALL) (Raaschou-Nielsen et al., 2008). A 2012 review of concluded that there was a link between radon exposure and childhood leukemia incidence in ecologic studies, and a weaker association across case-control studies (Tong et al., 2012a). A recent meta-analysis of case-control studies in Europe found 43% higher odds (95% confidence interval, 95%CI: 1.19, 1.72) of childhood leukemia from radon exposure (Ngoc et al., 2023).

Outside of an Iowa ecologic study (Smith et al., 2007) and two small case control studies (Steinbuch et al., 1999; Lubin et al., 1998), no other studies were found on radon exposure and childhood cancer risk in the U.S. In this ecologic study, our objectives were to estimate associations by applying spatiotemporal epidemiological methods to model annual incident cancer risk and radon exposures in a large sample of counties in the U.S. over a multi-decade period.

Section snippets

Methods

Children ages 0–19 living in counties with registries reporting to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) database, covering approximately 48% of the U.S. population (National Cancer Institute, 2024b), were included in this study. Ascertainment of cancers in SEER is systematic and high-quality, with over 98% completeness for malignant primary tumors (U.S. Department of Health and Human Services - Office of Disease Prevention and Health

Results

In the 727 U.S. counties comprising the study sample at baseline, 81.9% of adults in the counties had at least a high school education, and median household incomes averaged $45,228 (Table 1). The average population aged 0–19 years in these counties was 41,599 people, the density of the population averaged 331 people/km2, the elevation averaged 397 m, and the average temperature was 13.2 degrees Celsius (55.8 degrees Fahrenheit). Counties that were exposed to higher levels of radon tended to

Discussion

In this largest ecologic analysis of radon exposure and childhood cancer incidence in the U.S. to-date, we observed elevated risks of leukemia associated with prior year radon exposure. There were also some differences by sex. A uniquely applied Bayesian spatiotemporal framework permitted inclusion of counties with low or zero annual childhood cancer diagnoses, as well as intuitive risk estimation.

Radon-222, which is emitted above ground from underground sources, is the predominant domestic

Conclusion

In the largest study of radon and childhood cancer in the U.S. to date, we observed positive risk estimates for childhood leukemia in both sexes from average basement radon exposures the year prior. Therefore, there is strengthening rationale to further investigate links between radon and non-pulmonary cancers using a variety of robust designs, such as those that are population based and can incorporate individual level information. Deeper examination by cancer subtypes, sex, and exposure

Process to obtain data and code

Incident cancer data can be requested from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Radon data and code to conduct the analyses can be requested from the authors. Covariate data are publicly available.

CRediT authorship contribution statement

Matthew Bozigar: Writing – review & editing, Writing – original draft, Software, Methodology, Investigation, Formal analysis. Garyfallos Konstantinoudis: Writing – review & editing, Software, Methodology. Carolina L. Zilli Vieira: Writing – review & editing, Data curation. Longxiang Li: Writing – review & editing, Methodology, Data curation. Yazan Alwadi: Writing – review & editing, Resources, Data curation. Rena R. Jones: Writing – review & editing, Methodology. Petros Koutrakis: Writing –

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

GK is supported by an Imperial College Research Fellowship. RRJ's contributions are from the Intramural Research Program of the National Cancer Institute. This publication was made possible by U.S. EPA grant RD-835872. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the U.S. EPA. Further, U.S. EPA does not endorse the purchase of any commercial products or services mentioned in the publication.

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