Phytoestrogens (such as isoflavones and lignans) and organochlorine compounds (such as pesticides and polychlorinated biphenyls) are two broad classes of putative endocnne disruptors -- chemicals that may have the capability to alter a woman's hormonal milieu. The U.S. population is exposed to dietary sources of phytoestrogens through intake of soy foods, grains, and to a lesser extent fruits and vegetables. In addition, residues of organochlorine compounds can be detected in the tissue of a large proportion of the population. Mthough phytoestrogens and organochlorine compounds are suspected of being important environmental determinants of hormone-related neoplasia, there are few epidemiologic studies testing these hypotheses. Uterine fibroids are benign tumors whose growth is highly dependent on ovarian hormones, and are among the most frequently diagnosed neoplasms among women. As such, fibroids represent an ideal setting in which to test the hypothesis that environmental endocrine disruptors affect the risk of important female health outcomes. We propose to conduct a population-based case-control study to determine whether biomarkers of exposure to phytoestrogens and organochlorine compounds are related to a woman's risk of uterine fibroids. The study will be an ancillary investigation to The Uterine Leiomyomata Epidemiology Project (TULEP), an on-going study ended by the National Institutes of Child Health and Human Development. TULEP is being conducted within the population of Group Health Cooperative (GHC) of Puget Sound, a large pre-paid health plan. TULEP data collection includes an extensive in-person interview to assess medical, reproductive, menstrual, contraceptive, and other characteristics. For the proposed study, we will enroll from TULEP a subset of 175 premenopausal women with new, ultrasound-confirmed uterine fibroids (cases) and 175 premenopausal controls, frequency matched on age and race. From each of these women we will obtain a serum sample (for organochlorine analyses), an overnight urine sample (for phytoestrogen analyses), and food frequency questionnaires. In addition, in a sub-sample of 20 cases and 20 controls we will conduct an inter-method reliability study to compare phytoestrogen excretion in an overnight urine sample against a 24-hour urine sample. Serum samples will be analyzed for organochlorine residues (e.g., total PCBs, DDE, heptachlor epoxide, oxychlordane, frans-nonachlor, dieldrin, HCB, and beta-BHC) and total lipids using standard methods. Urine samples will be analyzed for excretion of isoflavones (daidzein, genistein, equol, and O-desmethylangolensin) and lignans (enterodiol and enterolactone) and urinary creatinine. Phytoestrogen excretion and organochlorine residues in cases and controls will be compared using multivariate unconditional logistic regression models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES008305-04
Application #
6055957
Study Section
Special Emphasis Panel (ZES1-CKS-B (M1))
Program Officer
Collman, Gwen W
Project Start
1996-09-01
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
Atkinson, Charlotte; Lampe, Johanna W; Scholes, Delia et al. (2006) Lignan and isoflavone excretion in relation to uterine fibroids: a case-control study of young to middle-aged women in the United States. Am J Clin Nutr 84:587-93
Atkinson, Charlotte; Skor, Heather E; Dawn Fitzgibbons, E et al. (2003) Urinary equol excretion in relation to 2-hydroxyestrone and 16alpha-hydroxyestrone concentrations: an observational study of young to middle-aged women. J Steroid Biochem Mol Biol 86:71-7
Atkinson, Charlotte; Skor, Heather E; Fitzgibbons, E Dawn et al. (2002) Overnight urinary isoflavone excretion in a population of women living in the United States, and its relationship to isoflavone intake. Cancer Epidemiol Biomarkers Prev 11:253-60
Schwartz, S M (2001) Invited commentary: Studying the epidemiology of uterine leiomyomata--past, present, and future. Am J Epidemiol 153:27-9; discussion 30
Schwartz, S M (2001) Epidemiology of uterine leiomyomata. Clin Obstet Gynecol 44:316-26
Schwartz, S M; Marshall, L M; Baird, D D (2000) Epidemiologic contributions to understanding the etiology of uterine leiomyomata. Environ Health Perspect 108 Suppl 5:821-7