Uterine leiomyomata (UL) are diagnosed in 25-30% of reproductive-aged women, resulting in considerable gynecologic morbidity and billions in U.S. health care costs annually. African Americans have 2-3 times the UL incidence of Whites and greater disease severity. Sex steroid hormones are involved in the etiology of UL. Given that endocrine disrupting chemicals (EDCs) can alter the functioning of hormones, we propose to evaluate UL risk in relation to 3 classes of EDCs: phthalates, polychlorinated biphenyls (PCBs), and phenols, specifically bisphenol A (BPA). Our choice of chemicals is informed by their high exposure prevalence in humans and by in vitro, animal, and human data documenting their effects on reproductive hormones and processes that could influence UL risk. Existing studies of EDCs and UL are limited by small sample size, uncertain temporality due to retrospective design, and suboptimal measurement of EDCs and UL. This study will use data and biospecimens from the Study of Environment Lifestyle and Fibroids (SELF), a NIEHS prospective cohort study of 1,300 African American women aged 23-34 and free of UL at baseline (2010-2012). Questionnaire data were collected at baseline and subjects are being followed for 5 years. Every 20 months, blood and urine are collected, and ultrasounds are performed by trained sonographers to detect UL. We request support for the laboratory and statistical analysis of EDCs in relation to UL incidence. We propose a cost-effective case-cohort study design that includes 400 incident UL cases and 400 controls. We will measure urinary phthalate metabolites, serum PCBs, and urinary BPA, characterize exposures according to UL risk factors, and determine the associations of these chemicals with UL incidence and tumor characteristics. Non-persistent chemicals (phthalates, BPA) will be measured at baseline, 20 months, and 40 months. Persistent chemicals (PCBs) will be measured at baseline only. SELF provides a unique opportunity to assess the association of common EDCs with UL risk. This project has many strengths that overcome the limitations of prior studies: large sample size, prospective data collection, state-of-the-art EDC measurement, serial ultrasound screening for UL, analysis of repeated EDC measures, innovative statistical approaches for evaluating EDC mixtures, and control for multiple confounders. Pilot data show large exposure variability, providing excellent power to test the proposed hypotheses. This study of African Americans, a high-risk population for EDC exposure and UL, will provide informative data on the effects of widespread pollutants on UL, seek explanations for the racial disparity in UL incidence, and provide critical data to the public, scientific community, and policy makers.

Public Health Relevance

Uterine leiomyomata (UL), or fibroids, are a major source of gynecologic morbidity among reproductive-aged women and African American women have 2-3 times the UL incidence of White women. We propose to investigate whether exposures to common endocrine-disrupting chemicals?phthalates, polychlorinated biphenyls (PCBs), and bisphenol A (BPA)?increase the incidence of UL in African American women. Our study overcomes the limitations of previous studies and will provide highly informative data on the effects of these widespread pollutants on UL that will be useful to the public, scientific community, and policy makers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
3R01ES024749-04S1
Application #
9626582
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Boyles, Abee
Project Start
2015-09-30
Project End
2020-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Boston University
Department
Public Health & Prev Medicine
Type
Organized Research Units
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code