Increased Ovarian Cancer Risk Linked to Elevated Nitrogen Dioxide Exposure, Study Finds

Greater levels of ambient nitrogen dioxide (NO₂) exposure may be associated with higher ovarian cancer incidence, according to a research letter published in Environmental Health Perspectives.¹

The researchers noted that outdoor air pollution is classified as a group 1 carcinogen, primarily due to associations with lung cancer.² However, it has increasingly been associated with a higher incidence of other cancers, like uterine and breast cancers.¹ Ovarian cancer shares a hormonal etiology with breast and uterine cancers, so they considered its association with outdoor air pollution.

Many past studies that evaluated the relationship between outdoor air pollution and ovarian cancer analyzed mortality rather than incidence. However, one recent study found a positive association between county-level estimates of ambient particulate matter (PM_2.5) and ovarian cancer incidence.³ Building upon this literature, the researchers investigated the association between individual-level residential estimates of air pollution (NO₂, PM_2.5, and ozone [O₃]) and incident ovarian cancer.¹

Higher levels of ambient nitrogen dioxide may be linked to an increased incidence of ovarian cancer. | Image Credit: hramovnick - stock.adobe.com

To do so, they analyzed patients from the Sister Study (2003-2009), which enrolled 50,884 women across the US between the ages of 35 and 74 years with at least 1 sister who had breast cancer but no prior breast cancer themselves. However, they excluded those who withdrew, had missing data, or had a history of ovarian cancer or bilateral oophorectomy at baseline; this resulted in 40,308 eligible women.

Among the study population, ovarian cancer diagnoses were self-reported during annual follow-up surveys and confirmed using medical records when available. Also, the researchers estimated 12-month average ambient concentrations of NO₂, PM_2.5, and O₃ over the follow-up period at the participants’ primary residential addresses.

Then, they used Cox proportional hazards models to estimate HRs for ovarian cancer based on increased pollutant levels, adjusting for various risk factors, including race/ethnicity, neighborhood socioeconomic status, and reproductive history. Additionally, the study explored how menopausal status, US Census region, and residential urbanicity influenced this relationship.

During the mean (standard deviation [SD]) follow-up time of 9.8 (2.5) years, 249 of the 40,308 participants were diagnosed with ovarian cancer. According to the US Census, 31.3% (n = 78) lived in the South, 29.3% (n = 73) in the Midwest, 23.7% (n = 59) in the West, and 15.7% (n = 39) in the Northeast.

The researchers found that a 5 parts per billion (ppb) increase in NO₂ was associated with a higher incidence of ovarian cancer (HR, 1.21; 95% CI, 1.04-1.41). This association remained consistent after adjusting for co-pollutants (HR, 1.21; 95% CI, 0.99-1.47) and ovarian cancer risk factors (HR, 1.17; 95% CI, 0.95-1.43).

Conversely, after adjusting for co-pollutants, PM_2.5 was not linked to ovarian cancer (HR, 1.02; 95% CI, 0.65-1.60). However, there were elevated but imprecise estimates among premenopausal women (HR, 2.85; 95% CI, 0.98-8.29) and those living in either the Midwest (HR, 1.40; 95% CI, 0.40-4.89) or West (HR, 1.63; 95% CI, 0.75-3.52).

Similarly, a heightened association between ovarian cancer and O₃ exposure was discovered during premenopausal years (HR, 1.36; 95% CI, 0.88-2.10), but no association was observed otherwise.

The researchers acknowledged their study’s limitations, including that it had limited power to explore ovarian cancer histotypes or relevant subgroups. Also, the exposure estimates do not capture air pollution indoors or away from the home. Despite their limitations, they suggested areas for future research based on their findings.

“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,” the authors concluded.

References

1. Ish JL, Chang CJ, Bookwalter DB, et al. Outdoor air pollution exposure and ovarian cancer incidence in a United States-wide prospective cohort study. Environ Health Perspect. 2024;132(10):107701. doi:10.1289/EHP14729
2. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans Outdoor air pollution. IARC Monogr Eval Carcinog Risks Hum. 2016;109:9-444.
3. Kentros PA, Huang Y, Wylie BJ, et al. Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: an ecological study. BJOG. 2024;131(5):690-698. doi:10.1111/1471-0528.17689