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Peer-reviewedCC BY 4.0Journal of Exposure Science & Environmental Epidemiology

Long-term outdoor air pollution and risk of ovarian and endometrial cancers in a large prospective cohort

  • Samantha Ammons1
  • Jared A. Fisher1
  • Jessica M. Madrigal1
  • Lauren M. Hurwitz1
  • Joel D. Kaufman2
  • Alexandra J. White3
  • Britton Trabert4
  • Debra T. Silverman1
  • Katie M. Applebaum5
  • Megan A. Clarke6,7
  • Rena R. Jones1
7 affiliations
  1. 1Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), National Institutes of Health (NIH), Rockville, MD USA
  2. 2Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA USA
  3. 3Epidemiology Branch, Chronic Disease Epidemiology Group, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC USA
  4. 4Department of Obstetrics and Gynecology, Fox Spencer Eccles School of Medicine, University of Utah, and Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT USA
  5. 5Department of Environmental and Occupational Health, The George Washington University, Milken Institute School of Public Health, Washington, DC USA
  6. 6Clinical Genetics Branch, DCEG, NCI, NIH, Rockville, MD USA
  7. 7AbbVie Inc, North Chicago, IL USA
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Abstract

Background: Outdoor air pollution is a known human carcinogen, but studies of female reproductive malignancies other than breast cancer remain limited.

Objective: We evaluated associations between outdoor air pollutants and risk of two gynecologic cancers

Methods: Using nationwide spatiotemporal models, we estimated outdoor residential fine particulate matter (PM2.5, < 2.5 µm) and nitrogen dioxide (NO2) concentrations for 140,457 female NIH-AARP Diet and Health Study participants (enrolled 1995–1996), with follow-up through 2018. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations between time-varying, 5-year average PM2.5 and NO2 concentrations (per 5 µg/m3 and ppb, respectively; 1980–2017) and incident endometrial (n = 3088) and ovarian (n = 1582) cancers, overall and by histologic subtype. Models were adjusted for age and demographic, lifestyle, and neighborhood factors. We evaluated co-pollutant adjustment and effect modification by state (per state-specific interquartile ranges), neighborhood deprivation, and body mass index (BMI).

Results: We found no relationships with risk of either cancer overall. PM2.5 was associated with endometrial cancer among participants in Atlanta, Georgia (HR:1.70, CI = 1.16–2.48) and Pennsylvania (HR:1.15, CI = 1.02–1.29). A weaker NO2 association was apparent in these areas (HR:1.57, CI = 1.11–2.22 and HR:1.10, CI = 0.94–1.28, respectively). Associations with endometrial cancer were suggested in the highest quintile of neighborhood deprivation (HR PM2.5: 1.05; CI = 0.90–1.22; p-trend=0.07) and HR NO2:1.06, CI = 1.00–1.12; p-trend=0.02. We found positive, albeit imprecise, ovarian cancer associations in Detroit, Michigan (PM2.5 HR:1.42, CI = 0.92–2.18 and NO2 HR:1.72, CI = 0.95–3.13). NO2 was positively associated with non-endometrioid endometrial cancers (HR:1.12, CI = 0.94–1.35) and PM2.5 with non-epithelial ovarian tumors (HR:1.50, CI = 0.91–2.47). The impact of co-pollutant adjustment varied across state-specific associations. Relationships did not vary by BMI.

Significance: We demonstrated modest relationships between air pollutants and risk of endometrial and ovarian cancers for select geographies, neighborhood characteristics, and histologic subtypes. Our findings indicate that future studies should evaluate region-specific factors, including co-varying pollutant distributions.

Impact Statement: Research on endometrial and ovarian cancers has primarily focused on risk factors such as body mass index and exposure to exogenous and endogenous hormones, particularly unopposed estrogen. We identified suggestive associations between these two cancers and outdoor air pollution exposures, specifically PM2.5 and NO2, in specific geographic regions and for certain histologic subtypes. Our novel findings suggest that PM2.5 chemical constituency and the region-specific air pollution mixture may play a role in the development of these cancers and warrants future investigation.

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Cite

BibTeXRIS
BibTeX
@article{ammons2026longterm,
  title = {{Long-term outdoor air pollution and risk of ovarian and endometrial cancers in a large prospective cohort}},
  author = {Samantha Ammons and Jared A. Fisher and Jessica M. Madrigal and Lauren M. Hurwitz and Joel D. Kaufman and Alexandra J. White and Britton Trabert and Debra T. Silverman and Katie M. Applebaum and Megan A. Clarke and Rena R. Jones},
  journal = {Journal of Exposure Science \& Environmental Epidemiology},
  year = {2026},
  month = jun,
  doi = {10.1038/s41370-026-00901-7},
  url = {https://doi.org/10.1038/s41370-026-00901-7},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Long-term outdoor air pollution and risk of ovarian and endometrial cancers in a large prospective cohort
AU  - Samantha Ammons
AU  - Jared A. Fisher
AU  - Jessica M. Madrigal
AU  - Lauren M. Hurwitz
AU  - Joel D. Kaufman
AU  - Alexandra J. White
AU  - Britton Trabert
AU  - Debra T. Silverman
AU  - Katie M. Applebaum
AU  - Megan A. Clarke
AU  - Rena R. Jones
PY  - 2026
DA  - 2026/06/15
JO  - Journal of Exposure Science & Environmental Epidemiology
DO  - 10.1038/s41370-026-00901-7
UR  - https://doi.org/10.1038/s41370-026-00901-7
AB  - Background: Outdoor air pollution is a known human carcinogen, but studies of female reproductive malignancies other than breast cancer remain limited.  Objective: We evaluated associations between outdoor air pollutants and risk of two gynecologic cancers  Methods: Using nationwide spatiotemporal models, we estimated outdoor residential fine particulate matter (PM2.5, < 2.5 µm) and nitrogen dioxide (NO2) concentrations for 140,457 female NIH-AARP Diet and Health Study participants (enrolled 1995–1996), with follow-up through 2018. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations between time-varying, 5-year average PM2.5 and NO2 concentrations (per 5 µg/m3 and ppb, respectively; 1980–2017) and incident endometrial (n = 3088) and ovarian (n = 1582) cancers, overall and by histologic subtype. Models were adjusted for age and demographic, lifestyle, and neighborhood factors. We evaluated co-pollutant adjustment and effect modification by state (per state-specific interquartile ranges), neighborhood deprivation, and body mass index (BMI).  Results: We found no relationships with risk of either cancer overall. PM2.5 was associated with endometrial cancer among participants in Atlanta, Georgia (HR:1.70, CI = 1.16–2.48) and Pennsylvania (HR:1.15, CI = 1.02–1.29). A weaker NO2 association was apparent in these areas (HR:1.57, CI = 1.11–2.22 and HR:1.10, CI = 0.94–1.28, respectively). Associations with endometrial cancer were suggested in the highest quintile of neighborhood deprivation (HR PM2.5: 1.05; CI = 0.90–1.22; p-trend=0.07) and HR NO2:1.06, CI = 1.00–1.12; p-trend=0.02. We found positive, albeit imprecise, ovarian cancer associations in Detroit, Michigan (PM2.5 HR:1.42, CI = 0.92–2.18 and NO2 HR:1.72, CI = 0.95–3.13). NO2 was positively associated with non-endometrioid endometrial cancers (HR:1.12, CI = 0.94–1.35) and PM2.5 with non-epithelial ovarian tumors (HR:1.50, CI = 0.91–2.47). The impact of co-pollutant adjustment varied across state-specific associations. Relationships did not vary by BMI.  Significance: We demonstrated modest relationships between air pollutants and risk of endometrial and ovarian cancers for select geographies, neighborhood characteristics, and histologic subtypes. Our findings indicate that future studies should evaluate region-specific factors, including co-varying pollutant distributions.  Impact Statement: Research on endometrial and ovarian cancers has primarily focused on risk factors such as body mass index and exposure to exogenous and endogenous hormones, particularly unopposed estrogen. We identified suggestive associations between these two cancers and outdoor air pollution exposures, specifically PM2.5 and NO2, in specific geographic regions and for certain histologic subtypes. Our novel findings suggest that PM2.5 chemical constituency and the region-specific air pollution mixture may play a role in the development of these cancers and warrants future investigation.
SN  - 1559-0631
SN  - 1559-064X
ER  -