Nitrogen Dioxide Exposure Linked to Increased Ovarian Cancer Risk

Nitrogen dioxide (NO₂) is a risk factor for ovarian cancer, according to a study recently published in Medicine, suggesting that exposure may accelerate the onset and progression of the disease.¹

Assessing Air Pollution’s Impact on Ovarian Cancer

Previous research has indicated that long-term exposure to air pollution, particularly NO₂, may contribute to ovarian cancer development by inducing oxidative stress, inflammatory responses, and DNA damage. However, studies examining the relationship between NO₂ and ovarian cancer have been limited by small sample sizes and unclear causal links. To address these gaps, the researchers conducted a Mendelian randomization (MR) analysis combined with a meta-analysis to explore the causal relationship between air pollution and ovarian cancer.

The MR analysis examined 5 air pollution indices using ovarian cancer data from 2 sources. The first, the FinnGen R10 database, included 184,018 participants (1091 cases; 182,927 controls) and 21,292,905 single-nucleotide polymorphisms (SNPs).² The second, the Open Genome-Wide Association Studies (OpenGWAS) database from the Ovarian Cancer Association Consortium, comprised 66,450 participants (25,509 cases; 40,941 controls) and 15,594,303 SNPs.³

The researchers performed a meta-analysis of the primary inverse-variance weighted (IVW) results, with multiple corrections to ensure accuracy.¹ This was followed by a reverse causality MR analysis.

NO₂ Identified As a Significant Risk Factor for Ovarian Cancer

Only NO₂ showed a significant association with ovarian cancer. Commonly found in atmospheric pollutants, NO₂ is a toxic gas produced by the oxidation of nitric oxide, characterized by its irritant and oxidative properties. Sources include natural processes, such as volcanic activity, forest fires, and bacterial activity, as well as human activities, including vehicle emissions, fossil fuel combustion, and industrial processes. Long-term exposure can lead to respiratory diseases and increase the risk of heart disease, stroke, and cancer.⁴

In the FinnGen R10 database, the IVW analysis yielded an OR of 2.618 (95% CI, 1.066-6.432; P = .0358), with a β value of 0.963.¹ The MR-Egger and weighted median methods produced consistent β values of 1.017 and 0.843, respectively, indicating NO₂ as a risk factor for ovarian cancer.

Similarly, in the OpenGWAS database, the IVW analysis showed an OR of 1.466 (95% CI, 1.106-1.943; P = .0078), with a β value of 0.383. Additionally, the MR-Egger and weighted median analyses yielded β values of 0.758 and 0.408, respectively. All 3 β values were directionally consistent, reinforcing NO₂’s association with ovarian cancer.

A meta-analysis of IVW results from both datasets, with multiple P-value corrections, confirmed the association between NO₂ and ovarian cancer (OR, 1.544; 95% CI, 1.180-2.020; P = .0077). However, the reverse MR analysis found no evidence that ovarian cancer increases NO₂ exposure, with ORs of 1.095 (95% CI, 0.991-1.209; P = .074) in the FinnGen R10 database and 1.0185 (95% CI, 0.980-1.055; P = .080) in the OpenGWAS database.

Translating Findings Into Policy and Prevention

The researchers concluded by acknowledging their limitations, including that the study population was primarily of European descent, which may limit generalizability. Still, they emphasized the study’s significance.

“…this study provides important evidence for the formulation of public health policies and the understanding of the risk posed by air pollution to ovarian cancer, driving the implementation of stricter air quality standards and offering new perspectives for prevention and intervention strategies for high-risk populations,” the authors wrote. “By reducing NO2 concentrations in the air, public health can be significantly improved, and the incidence of ovarian cancer can be reduced.”

References

1. Yi W, Feng X, Yang J. Causal validation of the relationship between air pollution and ovarian cancer: a bidirectional Mendelian randomization study and meta-analysis. Medicine (Baltimore). 2025;104(46):e45841. doi:10.1097/MD.0000000000045841
2. Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508-518. doi:10.1038/s41586-022-05473-8
3. Phelan CM, Kuchenbaecker KB, Tyrer JP, et al. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017;49(5):680-691. doi:10.1038/ng.3826
4. Huang S, Li H, Wang M, et al. Long-term exposure to nitrogen dioxide and mortality: a systematic review and meta-analysis. Sci Total Environ. 2021;776:145968. doi:10.1016/j.scitotenv.2021.145968