Multiple primary cancer incidence by county-level smoking prevalence among U.S. cancersurvivors

Background: As the number of cancer survivors in the U.S. grows, multiple primary cancer (MPC) has become an increasing public health concern. Understanding geographic variation in MPC incidence can inform targeted public health strategies. In this study, we aimed to examine associations between MPC incidence and county-level smoking prevalence. Methods: We conducted a retrospective cohort study using data from the SEER 17 registries, representing 26.5% of the U.S. population. The cohort included 6,364,027 individuals diagnosed with an initial primary cancer between 2000 and 2021, followed through December 2021. County-level smoking prevalence was the primary exposure. The main outcome was MPC incidence, assessed using observed-to-expected ratios (OERs) across strata of smoking prevalence. Analyses were stratified by sex, age, and race/ethnicity. Results: OERs of MPC increased with higher county-level smoking prevalence, from 1.05 (95% CI=1.04, 1.06) among males and 1.26 (95% CI=1.24, 1.27) in females in low-prevalence counties to 1.29 (95% CI=1.13, 1.14) and 1.61 (95% CI=1.40, 1.85), respectively, in high-prevalence counties. Robust relationships were observed among individuals diagnosed with their initial cancer at ages 45–64. Conclusions: County-level smoking prevalence is positively associated with MPC incidence. These findings support the need for targeted, community-level tobacco control interventions to reduce MPC risk. Impact: By linking county-level smoking prevalence to MPC risk, this study highlights the potential utility of community-level data in identifying high-risk populations and guiding tobacco control and survivorship interventions.