Background: Radon and smoking synergistically increase risk of lung cancer, particularly for small cell and squamous cell carcinoma; however, associations by sex and race/ethnicity have not been reported.

Methods: We used data from the Behavioral Risk Factor Surveillance System (BRFSS), Environmental Protection Agency (EPA), and SEER21, excluding Alaska, to investigate the associations between county-level radon and smoking prevalence with lung cancer incidence by histotype, sex, and race/ethnicity (2006-2016). We only examined Non-Hispanic (NH) White and NH Black race/ethnicities due to the small proportion of cases from other groups. We used tertiles of sex-specific smoking prevalence estimates (1996-2000) from the BRFSS and EPA-defined radon zones of low, moderate, and high, to categorize 729 counties by both radon levels and smoking prevalence by sex. We fit generalized linear models using modified Poisson regression with Huber-White robust standard errors to compute rate ratios (RRs) and 95% confidence intervals (CIs) associating radon exposure, stratified by smoking tertile with histotype-specific lung cancer incidence.

Results: The smoking prevalence captured by each tertile was considerably lower for women (Low=9.0-22.4%, Moderate>22.4-25.3, High>25.3-36.6) than men (Low=14.4-27.3, Moderate>27.3-31.6, High>31.6-40.3). Among women, we observed the most pronounced associations between high radon and lung cancer risk compared to low radon within the highest female smoking tertile. These associations were evident among NH Black women, particularly for small cell carcinoma (RR=1.34, 95% CI: 1.05-1.71) and squamous cell carcinoma (RR=1.41, CI: 1.14-1.74), but were smaller and non-significant among NH White women. For men, the associations with radon were observed even in counties with low male smoking prevalence. For example, in counties in the lowest tertile of male smokers, associations of high radon with squamous cell and small cell lung cancer were observed among NH Black men (RR=1.27, 95% CI: 1.11-1.44, and RR=1.37, 95% CI:1.15-1.63, respectively) and NH White men (RR=1.18, 95% CI: 1.11-1.26, and RR=1.20, 95% CI: 1.11-1.29, respectively). When we considered that the percent of current smokers in the lowest smoking tertile for men overlaps the highest tertile for women, we observed radon-associated small cell and squamous cell lung cancer risk for NH Black men and women at comparable absolute smoking prevalence, and a similar but attenuated pattern in NH White men and women.

Discussion: While our analysis is limited by the ecological nature of the radon and smoking data, this research suggests that previously reported associations between radon and smoking exposure and histotype-specific lung cancer risk may differ by race and sex. Further research is needed to understand the impact of combined radon and smoking exposure on lung cancer risk in other racial and ethnic groups.

Citation Format: Rachel McCarty, Lindsay Collin, Laurie Grieshober, Judy Ou, Carol Sweeney, Mollie E. Barnard, Jennifer A. Doherty. County-level radon and smoking exposure and lung cancer risk by histotype, sex, and race/ethnicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 795.