Epidemiologic research on environmental chemical exposures and ovarian and endometrial cancers: a systematic review

Endometrial cancer (EC) and ovarian cancer (OC) are the most diagnosed gynecologic malignancies in the U.S. Environmental exposures are biologically plausible risk factors but remain understudied, and synthesis of these relationships is lacking. We systematically searched for epidemiologic studies evaluating associations between environmental chemical exposures and EC and/or OC incidence and mortality. Among 145 studies that met inclusion criteria, over half were focused on investigation of OC only (N = 78; 54%), were conducted in North America (N = 75; 53%), and most used a cohort design (N = 58; 40%). Outdoor air pollution (N = 27; 18%) and ultraviolet light (N = 22; 15%) were the most represented exposures, followed by pesticides (N = 16; 11%). We conducted a meta-analysis of seven studies of the most frequently investigated pollutant, fine particulate matter (PM_2.5), including two studies of OC, three of EC, and two studies evaluating both cancers. There was no evidence of a meta-association for PM_2.5 and OC based on four studies (HR_meta per 5 μg/m³ = 1.02, 95%CI = 0.91-1.13); this finding was consistent among the three studies that mutually adjusted for co-pollutants (HR_meta per 5 μg/m³ = 0.94, 95%CI = 0.81-1.09). For EC, the summary estimate from five studies was weakly elevated overall (HR _meta = 1.02, 95%CI = 0.99-1.05) and in analyses limited to studies with co-pollutant adjustment (HR _meta = 1.01, 95%CI = 1.00-1.01) or incident cases only (HR = 1.01, 95%CI = 1.01-1.02). Our review confirms the sparse literature on environmental risk factors for these cancers and notable heterogeneity in exposures studied. Relatively limited investigation of EC is an important research gap given its unexplained rising incidence in population subgroups within the U.S. and globally.