A familiar paradox in a new exposure: Electronic cigarettes and thyroid cancer.

Abstract

e22601 Background: Electronic cigarette (e-cigarette) use has increased rapidly in recent years, particularly among younger adults, yet its long-term oncologic implications remain poorly characterized. While combustible cigarette smoking has paradoxically been associated with a lower risk of thyroid cancer, potentially related to hormonal suppression and immunomodulatory effects, evidence regarding the association between e-cigarette use and thyroid cancer is limited. We evaluated the association between e-cigarette use and thyroid cancer in a large, diverse U.S. population. Methods: We performed a cross-sectional analysis of adults participating in the NIH All of Us Research Program. E-cigarette exposure was defined using self-reported survey data and categorized as ever versus never use, with additional stratification into never, former, and current use. The primary outcome was thyroid cancer, identified using validated electronic health record diagnosis codes from the All of Us Registered Tier Dataset (version 8). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between e-cigarette use and thyroid cancer. Models accounted for age, sex, race and ethnicity, body mass index, alcohol use, and traditional cigarette smoking. Results: Among over 300,000 participants, 29,343 (8.9%) reported e-cigarette use. Compared with non-users, e-cigarette users were significantly younger (mean age: 45.2 vs 59.1 years) and differed across sex, race, and ethnicity, and multiple socioeconomic characteristics (p<0.001). After multivariable adjustment, ever e-cigarette use was associated with lower odds of thyroid cancer (OR 0.79, 95% CI 0.66-0.94). Current e-cigarette use demonstrated a stronger inverse association (OR 0.66, 95% CI 0.45-0.94), whereas former use was not statistically significant. Conventional cigarette smoking was independently associated with lower odds of thyroid cancer. No significant interaction between e-cigarette use and smoking status was observed. Conclusions: In this large population-based analysis, e-cigarette use was independently inversely associated with thyroid cancer after adjustment for established risk factors, mirroring prior observations reported for combustible cigarette smoking. These findings should not be interpreted as endorsement of e-cigarette use but suggest that nicotine-related or immunomodulatory pathways common to both exposures may influence thyroid carcinogenesis. Further prospective and mechanistic studies are needed to clarify causality and identify potential targets that can be leveraged without the harms associated with nicotine exposure.