Final Report: Persistent Organic Pollutants and Endometriosis Risk

EPA Grant Number: R829438
Title: Persistent Organic Pollutants and Endometriosis Risk
Investigators: Holt, Victoria L. , Barr, Dana Boyd , Chen, Chu
Institution: Fred Hutchinson Cancer Research Center
EPA Project Officer: Hunt, Sherri
Project Period: March 25, 2002 through March 24, 2005 (Extended to March 24, 2007)
Project Amount: $966,841
RFA: Endocrine Disruptors: Epidemiologic Approaches (2001) RFA Text |  Recipients Lists
Research Category: Endocrine Disruptors , Health , Safer Chemicals

Objective:

Endometriosis, defined as the implantation of endometrial glands and stroma outside of the uterine cavity, is a relatively common abnormality, that, in many women, may be a serious and chronic gynecologic disease with symptoms including severe pelvic and menstrual pain, dyspareunia, and infertility. There has been recent scientific and popular press speculation that exposure to chemicals affecting endocrine function may be an important risk factor for endometriosis, however little epidemiologic research has been done to investigate this hypothesis. The goal of this project is to assess the prevalence of exposure to organic pollutants in endometriosis cases and controls in a large health maintenance organization in western Washington state and to examine the interactions of these exposures with polymorphisms in genes involved in estrogen metabolism. Our specific aims were to:

  1. determine whether the risk of endometriosis is associated with lipid-adjusted serum levels of organochlorine pesticides
  2. determine whether the risk of endometriosis is associated with lipid-adjusted serum levels of polychlorinated biphenyls (PCBs)
  3. determine whether the risk of endometriosis resulting from organochlorine pesticide or PCB exposure differs among women with differing CYP1A1, CYP1A2, and GSTM1 genotypes; and This study was an ancillary investigation to Women’s Risk of Endometriosis (WREN), a case-control study funded by the National Institute of Child Health and Human Development.

Summary/Accomplishments (Outputs/Outcomes):

Subject self-report of any use of all types of pesticides combined was not associated with endometriosis risk overall (OR 0.93, 95% CI 0.69, 1.25). There was an indication of increased risk among those with exposure to herbicides (OR 1.51, 95% CI 0.98, 2.34) or fungicides (OR 2.02, 95% CI 0.97, 4.23), but these risks were not statistically significantly different from 1. Any self-reported exposure to fungicides was associated with a significantly increased endometriosis risk among GSTM1 not-null subjects (OR 4.47, 95% CI 1.04, 19.1) and CYP 1A1 TC and CC subjects (OR 6.50.95% CI 1.02, 41.27). Any self-reported herbicide exposure was associated with a significantly elevated disease risk among CYP 1A1 M2 AA subjects (OR 1.70, 95% CI 1.03, 2.80), CYP 1A2 intron AA subjects (OR 2.05, 95% CI 1.03, 3.88), and CYP 1A2 flank GG subjects (OR 1.72, 95% CI 1.05, 2.82).

Serum levels in the higher two tertiles were associated with increased endometriosis risk for PCBs 74 (OR 1.54, 95% CI 1.05, 2.24) and 118 (OR 1.41, 95% CI 0.97, 2.06). Higher levels of PCB 153 were associated with increased endometriosis risk among CYP 1A1 M1 TC and CC subjects (OR 2.81, 95% CI 1.05, 7.52), as were higher levels of PCB 146 among CYP 1A2 intron AC and CC subjects (OR 1.81, 95% CI 1.00, 3.30). Nonsignificantly increased endometriosis risk was seen among subjects with higher levels of β-hexachlorocyclohexane (OR 1.47, 95% CI 0.99, 2.18). In analyses of GSTM1 null subjects significant associations were seen for higher levels of o,p’-dichlorodiphenyl trichloroethane (OR 2.30, 95% CI 1.05, 5.03), and trans-nonachlor (OR 1.77, 95% CI 1.03, 3.05), and among CYP 1A1 M1 TC and CC subjects, higher levels of p,p’- dichlorodiphenyl dichloroetheylene were associated with increased disease risk (OR 2.38, 95% CI 1.02, 5.58).

Conclusions:

In this epidemiologic study of a U.S. health maintenance organization population of 18- 49 year old women, we found that self-reported exposure to fungicides and herbicides was associated with 1.5 to 2 fold risk of endometriosis. While this finding may be due in part to differential recall of past exposures between cases and controls or to chance, it suggests that chemical exposure at the general population level may be of modest concern in terms of this estrogen-dependent disease. Additionally, while in general PCB and pesticide serum levels in this population were not significantly associated with disease risk, there was a suggestion that higher levels of PCBs 74, 118, and 153 and β- hexachlorocyclohexane may be associated with increased risk of endometriosis, particularly in population sub-groups defined by certain genetic polymorphisms. This finding is not subject to recall bias, and if replicated in larger studies, may indicate that levels of these substances are high enough in the general population of reproductiveage women to affect health.

While results were adjusted for age and serum lipids, other noncausal explanations may exist for the associations seen. Further research in this area is warranted.

Journal Articles:

No journal articles submitted with this report: View all 4 publications for this project

Supplemental Keywords:

Molecular epidemiology,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Genetics, Environmental Chemistry, Chemistry, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Physical Processes, Children's Health, genetic susceptability, Endocrine Disruptors - Human Health, health effects, risk assessment, interindividual variability, puberty, reproductive effects, pesticide exposure, vulnerability, adolescence, health risks, racial and ethnic differences, adolescents, age-related differences, gene-environment interaction, endocrine disrupting chemicals, exposure, gender, pesticides, fertility, human malformation, children, particle exposure models, environmental mutagens, susceptibility, toxicity, cumulative environmental exposure, estrogen metabloism, human exposure, endocrine disrupting chemcials, environmental stressors, environmental toxicant, harmful environmental agents, race ethnicity, toxic environmental contaminants, diet, growth & development, endometriosis, reproductive health, toxicants, biological markers, exposure assessment, genetic diversity, reproductive, subpopulations, age, developmental disorders, human health risk

Progress and Final Reports:

Original Abstract
2002 Progress Report
2003 Progress Report
2004 Progress Report
2005 Progress Report