NIH grant: PAH exposure during reproductive windows of susceptibility and long-term chronic disease risk (1R01ES038509-01)

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NIH grant 1R01ES038509-01: PAH exposure during  reproductive windows of susceptibility and long-term chronic disease risk
Institute: {'code': 'ES', 'abbreviation': 'NIEHS', 'name': 'National Institute of Environmental Health Sciences', 'admin_org_id': '12500022', 'admin_funding_url': ''}. PI: Rebecca D Kehm. Award: $818402.
Start: 2026-07-02T00:00:00.
Chronic diseases such as cardiovascular disease (CVD) and cancer are the leading causes of death and
disability worldwide, with women experiencing a disproportionate burden. Breast cancer is the most common
cancer globally and accounts for two-thirds of all cancer cases in adults under 40. Women also experience higher
rates of several forms of CVD compared to men, and CVD often present differently in women, with distinct
symptoms and clinical manifestations. These differences highlight a critical gap in our understanding of how sex-
specific risk factors and life course exposures contribute to chronic disease in women. Studying reproductive
windows of susceptibility (WOS), such as pregnancy and perimenopause, may be particularly imporant because
they involve profound hormonal, metabolic, and physiological changes that may increase women’s vulnerability
to exposures such as environmental toxicants. However, few longitudinal studies have examined how exposures
during these critical periods impact long-term disease risk, largely due to challenges in capturing time-specific
exposures and maintaining extended follow-up. This study aims to fill that gap by investigating whether exposure
to polycyclic aromatic hydrocarbons (PAH), common pollutants found in air pollution, tobacco smoke, and certain
foods, during these reporductive WOS is associated with biomarkers of chronic disease risk in midlife. To
investigate this, we will leverage the Columbia Center for Children’s Environmental Health Mothers and
Newborns Cohort, a prospective study of 543 urban women who have been followed since pregnancy and are
now entering perimenopause. In prior research using this cohort, we found that PAH exposure during pregnacny
was associated with breast tissue composition measured 15 years later using optical spectroscopy – a non-
invasive but not clinically validated method for risk assessment. Building on these preliminary findings, the
current study will use mammographic breast density, a clinically validated biomarker of breast cancer risk, as
our primary outcome (Aim 1). We will also evaluate associations with 10-year CVD risk (Aim 2), and accelerated
biological aging using validated DNA methylation clocks (Aim 3). Participants will attend two midlife clinic visits
for biospecimen collection and mammographic imaging, enabling the assessment of both cross-sectional
associations and within-person changes during perimenopause. Additionally, we will conduct untargeted
metabolomics profiling in a subset of participants to explore broader environmental exposures and underlying
biological pathways contributing to chronic disease risk. This will be the first prospective study to evaluate PAH
exposure during two distinct reproductive WOS in the same individuals. By integrating longitudinal exposure data
with validated biomarkers of breast cancer, CVD, and biological aging, this research will generate novel insights
into the long-term health impacts of environmental toxicants during critical life stages. Ultimately, findings from
this study will address a critical gap in women’s environmental health research and inform life course-based
prevention strategies to reduce the burden of chronic disease.

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