Grantee Research Project Results
2000 Progress Report: Environmental Exposures Related to Early Puberty
EPA Grant Number: R825816Title: Environmental Exposures Related to Early Puberty
Investigators: Wolff, Mary S. , Kabat, Geoffrey , Forman, Joel , Britton, Julie , Leleiko, Neal , Hochman, Sarah , Larson, Signe , Kadlubar, Fred F. , Berkowitz, Gertrud S. , Godbold, James , Kase, Nathan
Current Investigators: Wolff, Mary S. , Kabat, Geoffrey , Forman, Joel , Britton, Julie , Leleiko, Neal , Hochman, Sarah , Larson, Signe , Kadlubar, Fred F. , Wetmur, James G. , Berkowitz, Gertrud S. , Godbold, James , Kase, Nathan , Serra, Nicole
Institution: Mount Sinai School of Medicine
EPA Project Officer: Aja, Hayley
Project Period: January 16, 1998 through January 15, 2001
Project Period Covered by this Report: January 16, 1999 through January 15, 2000
Project Amount: $380,482
RFA: Issues in Human Health Risk Assessment (1997) RFA Text | Recipients Lists
Research Category: Environmental Justice , Human Health
Objective:
The objective of this research project is to investigate the potential effect of cumulative, multiple environmental exposures on onset of puberty, in particular, early breast and hair development, which may be associated with estrogenic exposures. An additional objective is to characterize the role of environmental exposures in racial/ethnic differences among girls, because these exposures affect onset of puberty.The main hypothesis is that hormonally active exposures hasten onset of puberty (specifically, high levels of organochlorines and low levels of dietary isoflavones). The cytochrome P450 and related metabolizing enzyme alter onset of puberty through a gene-environment mechanism. Supplementary hypotheses are that environmental exposures are higher among girls from minority groups, and that such exposures are mitigated by hormone-metabolizing enzymes.
Progress Summary:
Healthy 9-year-old girls from the Mount Sinai Pediatric Outpatient Clinic and the nearby Uptown Pediatric Practice were recruited from 1997 to 1998 from three different ethnic groups (54 African-American, 66 Caucasian, 72 Hispanic). Both recent and usual dietary intake and potential confounders (height, weight, physical activity) were recorded. Blood samples were obtained to be analyzed for organochlorines (DDE, PCBs) and hormone-metabolizing genes. Spot urine samples were obtained to be analyzed for isoflavones. Other environmental agents also were collected. Limited information was collected on early life events (i.e., birth weight, mother's weight at birth). Further birth information was obtained from the hospital's neonatal database, as well as from birth certificates for girls not born at Mount Sinai Hospital, which was obtained from the New York City Department of Health.
The outcomes pubertal stages of breast and hair development are being modeled in relation to body size, physical activity, and dietary factors; including food and nutrient intake and phytoestrogens. A unique phytonutrient database has been established to estimate phytoestrogen intake from the dietary questionnaire. Obesity and physical activity also are being examined as the traditional risk factors for puberty. Organochlorine analyses are still underway, but preliminary data show low levels (i.e., DDE in serum less than 2 ng/mL) but some variability in both DDE and PCBs, as well as modest correlations with birthweight. These analyses will be completed as funds allow.
Results to date show strong positive associations of pubertal onset with body mass index and African-American ethnicity. There was no effect of phytoestrogens (as lignans, isoflavones, flavonoids, and phytosterols) on pubertal onset; there is a significant effect of a very few food items and of three nutrients (vitamin C, saturated fat, magnesium) with pubertal onset, but the meaning of these associations is not yet clear. Analysis of phytoestrogens in urine have been completed, illustrating some differences among ethnic groups. Relationships of urinary metabolites with pubertal onset are being examined. Differences are evident in physical activity among ethnic groups, but relationships with pubertal onset are not statistically significant. The statistical analyses for birth outcomes and organochlorines have not been completed. Common polymorphisms (i.e., variants present in 20-50 percent of the population) have been determined in several genes that metabolize both hormones and environmental contaminants (CYP3A4, CYP3A5, CYP17, CYP1A2, CYP1B1). An association between CYP3A4 and pubertal onset, independent of race/ethnicity, has been found. The other gene variants were not associated with puberty. However, associations between these genes and birth weight have been examined; preliminary analyses indicate some associations. Therefore, the statistical analyses will be expanded to include these genes, and possibly determine polymorphisms in other genes (e.g., PON1/2 for which associations with birth size have been seen in another study.
Future Activities:
In the laboratory, the organochlorine analyses will be completed, and PON1 on the biologic samples will be determined.Journal Articles:
No journal articles submitted with this report: View all 6 publications for this projectSupplemental Keywords:
puberty, ethnic, environmental exposures, hormones, diet, phytoestrogens, risk factors, P450, PCB, DDE, PON1., Health, RFA, Scientific Discipline, Susceptibility/Sensitive Population/Genetic Susceptibility, Risk Assessments, Chemistry, genetic susceptability, Environmental Chemistry, Endocrine Disruptors - Human Health, Children's Health, endocrine disruptors, Genetics, health effects, toxicity, environmental mutagens, particle exposure models, toxic environmental contaminants, health risks, biological markers, environmental stressors, harmful environmental agents, age-related differences, growth & development, risk assessment, breast cancer, hispanics, human exposure, childhood cancer, diet, susceptibility, cumulative environmental exposure, fertility, adolescents, children, exposure, gender, reproductive effects, endocrine disrupting chemicals, age, reproductive, toxicants, environmental toxicant, gene-environment interaction, adolescence, reproductive health, isoflavones, developmental disorders, exposure assessment, human malformation, vulnerability, cancer risk, puberty, genetic diversity, interindividual variability, race ethnicity, subpopulationsRelevant Websites:
http://www.childenvironment.org/ Exit
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.