A prospective cohort study of ambient air pollution exposure and risk of uterine leiomyomata.

study questionTo what extent are ambient concentrations of particulate matter <2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) associated with risk of self-reported physician-diagnosed uterine leiomyomata (UL)? SUMMARY ANSWER: In this large prospective cohort study of Black women, ambient concentrations of O3, but not PM2.5 or NO2, were associated with increased risk of UL. WHAT IS KNOWN ALREADY: UL are benign tumors of the myometrium that are the leading cause of gynecologic inpatient care among reproductive-aged women. Black women are clinically diagnosed at two to three times the rate of white women and tend to exhibit earlier onset and more severe disease. Two epidemiologic studies have found positive associations between air pollution exposure and UL risk, but neither included large numbers of Black women. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study of 21 998 premenopausal Black women residing in 56 US metropolitan areas from 1997 to 2011. PARTICIPANTS/MATERIAL, SETTING,

methodsWomen reported incident UL diagnosis and method of confirmation (i.e. ultrasound, surgery) on biennial follow-up questionnaires. We modeled annual residential concentrations of PM2.5, NO2 and O3 throughout the study period. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for a one-interquartile range (IQR) increase in air pollutant concentrations, adjusting for confounders and co-pollutants. MAIN RESULTS AND THE ROLE OF CHANCE: During 196 685 person-years of follow-up, 6238 participants (28.4%) reported physician-diagnosed UL confirmed by ultrasound or surgery. Although concentrations of PM2.5 and NO2 were not appreciably associated with UL (HRs for a one-IQR increase: 1.01 (95% CI: 0.93, 1.10) and 1.05 (95% CI: 0.95, 1.16), respectively), O3 concentrations were associated with increased UL risk (HR for a one-IQR increase: 1.19, 95% CI: 1.07, 1.32). The association was stronger among women age <35 years (HR: 1.26, 95% CI: 0.98, 1.62) and parous women (HR: 1.28, 95% CI: 1.11, 1.48). LIMITATIONS, REASONS FOR CAUTION: Our measurement of air pollution is subject to misclassification, as monitoring data are not equally spatially distributed and we did not account for time-activity patterns. Our outcome measure was based on self-report of a physician diagnosis, likely resulting in under-ascertainment of UL. Although we controlled for several individual- and neighborhood-level confounding variables, residual confounding remains a possibility. WIDER IMPLICATIONS OF THE

findingsInequitable burden of air pollution exposure has important implications for racial health disparities, and may be related to disparities in UL. Our results emphasize the need for additional research focused on environmental causes of UL. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the National Cancer Institute (U01-CAA164974) and the National Institute of Environmental Health Sciences (R01-ES019573). L.A.W. is a fibroid consultant for AbbVie, Inc. and accepts in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com and Kindara.com for primary data collection in Pregnancy Study Online (PRESTO). M.J. declares consultancy fees from the Health Effects Institute (as a member of the review committee). The remaining authors declare they have no actual or potential competing financial interests. TRIAL REGISTRATION NUMBER: N/A.