Outdoor Air Pollution Exposure and Ovarian Cancer Incidence in a United States–Wide Prospective Cohort Study by Jennifer L. Ish, Che-Jung Chang, Deborah B. Bookwalter, Rena R. Jones, Katie M. O’Brien, Joel D. Kaufman, Dale P. Sandler, and Alexandra J. White, Oct 22, 2024, Environmental Health Perspectives Volume 132, Issue 10
CID: 107701
https://doi.org/10.1289/EHP14729
Introduction
Outdoor air pollution is classified as a Group 1 carcinogen based primarily on evidence of associations with lung cancer.1 It has increasingly been associated with a higher incidence of other cancers, including breast2,3 and uterine cancers.4 Ovarian cancer, which shares a hormonal etiology with breast and uterine cancers,5 is the deadliest gynecologic cancer among women, contributing to ∼12,740 deaths in the United States (US) in 2024.6
The literature on outdoor air pollution and ovarian cancer is sparse, with most studies evaluating mortality rather than incidence.7 The few studies investigating disease etiology utilize cross-sectional or ecologic designs focusing on area-level observations.7,8 A 2023 ecologic study using registry data across >700 US counties reported a positive association between county-level estimates of ambient particulate matter ≤2.5μm in aerodynamic diameter (PM2.5) and ovarian cancer incidence.8 Our study expands upon the existing literature by investigating the association between individual-level residential estimates of air pollution [nitrogen dioxide (NO2), PM2.5, and ozone (O3)] and incident ovarian cancer in a large, nationwide prospective cohort.
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Discussion
To our knowledge, our study is the first to report a positive association between individual-level ambient air pollution exposure and incident ovarian cancer. Using data from a large US-wide, prospective cohort with time-varying air pollution estimates accounting for residential mobility over follow-up, we found limited evidence of an association with PM2.5 or O3 exposure but observed that greater levels of ambient NO2 may be associated with higher ovarian cancer incidence. These findings are consistent with growing evidence for a role of air pollution, and for NO2 in particular, in the incidence of hormone-dependent female cancers, including breast2,3 and uterine cancer.4 Although the biologic pathways underlying potential impacts of NO2 exposure on ovarian cancer development are unclear, NO2 levels are considered a proxy for near-road pollutant mixtures containing numerous compounds (e.g., diesel exhaust, benzene, and polycyclic aromatic hydrocarbons) with known carcinogenic or endocrine disrupting effects.1
Although we found limited evidence for PM2.5 exposure overall, our findings suggest the association between PM2.5 exposure and ovarian cancer may vary by geographic region, which has previously been observed in breast cancer studies.3 These differences may reflect geographic variability in PM2.5 chemical composition due to different emission sources. Further, associations with PM2.5 and O3 exposure were more apparent for premenopausal person-time, which has also been reported for PM2.5 and NO2 exposure and breast cancer.11 Despite the large sample size, however, our study had limited power to explore relevant subgroups or consider histotypes. In addition, the exposure estimates do not capture air pollution indoors or exposures away from the home, although we expect such misclassification to be nondifferential.
In conclusion, our study provides evidence suggesting that exposure to NO2 may be a risk factor for ovarian cancer. Given the rarity of ovarian cancer, studies that pool data from multiple prospective cohorts are needed to examine associations by tumor characteristics or other potential modifiers, including PM2.5 chemical composition.
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