Grantee Research Project Results
1999 Progress Report: Reproductive Health, Serum Dixon, and P450 Genes in Vietnam Veterans
EPA Grant Number: R825817Title: Reproductive Health, Serum Dixon, and P450 Genes in Vietnam Veterans
Investigators: Sweeney, Anne , Symanski, Elaine , Denison, Michael , Cooper, Sharon , Wu, Xifeng , Junco, Deborah del
Current Investigators: Sweeney, Anne , Wun, Chuan-Chuan , Symanski, Elaine , Denison, Michael , Cooper, Sharon , Wu, Xifeng , Junco, Deborah del
Institution: The University of Texas at Houston
EPA Project Officer: Aja, Hayley
Project Period: November 19, 1997 through November 18, 2000 (Extended to November 30, 2002)
Project Period Covered by this Report: November 19, 1998 through November 18, 1999
Project Amount: $874,195
RFA: Issues in Human Health Risk Assessment (1997) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
Recent Institute of Medicine updates regarding the association of Agent Orange exposure and birth defects among the offspring of Vietnam veterans indicate a critical need to reexamine this controversial issue. The major limitations of previous studies were crude exposure assessment, selection bias, and small sample sizes. This is a nested case-control study to test hypotheses regarding dioxin exposure, the CYP1A1 variant allele, and any interactions between these two factors in producing pregnancies affected with a neural tube defect (NTD).Progress Summary:
A registry of all known 2.7 million male and female Vietnam veterans was obtained from the Departments of Defense and Veterans Affairs as the sampling frame. To maximize the probability of identifying veteran parents, the National Center for Health Statistics (NCHS), with the approval of State Vital Statistics Offices, provided birth and death certificate numbers for NTD births, deaths, and fetal deaths in the United States for the period 1962-1995. Parent identifiers are being abstracted from these certificates and cross-linked with the veteran registry for a list of "potential" matches (expected number=10,000), using the MatchWare software program. An interagency agreement with the National Institute for Occupational Health and Safety (NIOSH) and the Internal Revenue Service (IRS) has been established to provide current addresses for the veterans. A screening survey is currently being mailed to these potential matches, as well as to a subset of nonmatches (to account for the possibility of missing veterans in the registry) to determine eligibility based on both veteran and parental status. Cases are Vietnam veterans of an NTD-affected child; Vietnam veterans of healthy offspring serve as controls. An in-depth survey has been developed and will be sent to eligible participants for complete military and reproductive histories. A subset of 150 cases and 150 controls will be selected from this sample for dioxin and genetic polymorphism assays. This will be the first attempt to determine if a susceptibility gene exists for reproductive toxicity due to dioxin exposure.
The fifty states were trichotomized according to proportion of Vietnam veterans in the population, with Tier 1 having the highest proportion of veterans. A two-year effort has resulted in IRB approval from 40 states overall (80%): 10 of 10 in Tier 1; 16 of 17 in Tier 2; and 14 of 23 in Tier 3. Three states (Maryland, Arizona, and Virginia) denied access to any records; other states permitted access to only death certificates and still others allowed access to death, birth, and fetal death certificates for varying intervals. To date, we have ascertained 59,351 NTD records: 29,906 deaths, 16,460 births, and 12,985 fetal deaths from 33 states. Using Texas as a pilot state, parental information from 5,714 birth, death, and fetal death records were crossed with the veteran registry yielding 1,257 potential matches. Assuming successful contact with 60% of the veterans nationally, this will yield a sample of 856 NTD cases. Screening surveys are currently being mailed to identify eligible participants from all the participating states.
A meeting of the Advisory Board for this project was held at the University of Texas Houston School of Public Health on September 29, 1999. Six of the seven members participated in this meeting, the goals of which were to: 1) refine the in-depth survey that will assess military history (and thus potential exposure to Agent Orange) and 2) to discuss other potential genetic markers to examine in determining both exposure to dioxin and susceptibility to teratogenicity as a result of exposure to this contaminant. As a result of the contribution of these various experts, a concise and comprehensive military exposure survey was developed. In addition, it was decided that the genetic polymorphism assays would be expanded to include Ah receptor and CYP1B polymorphisms to the extent possible as determined by the budget allowance.
Future Activities:
During the current year, eligible participants selected from the screening survey will receive the in-depth survey to describe military history and reproductive experiences. In addition, a doctoral student here at the UT School of Public Health is conducting a study to examine the association between dioxin exposure and cancer, as well as any potential coexistence between birth defects and cancer in this population. An Exposure Index has been developed, with the assistance of the Advisory Board members, to categorize participants according to likelihood of exposure to dioxin (high, medium, or low probability). Cases and controls will be selected from within these strata for serum dioxin and genetic assays.
The establishment of the interagency agreement with NIOSH and the IRS was facilitated by the EPA, which serves as the official federal institution requesting this service. This agreement required several months to arrange; therefore the recruitment of participants was necessarily delayed until we could obtain the current addresses. A one-year extension of this project will be required to complete the case-control phase of the project.
Journal Articles:
No journal articles submitted with this report: View all 3 publications for this projectSupplemental Keywords:
exposure, risk assessment, teratogen, health effects, vulnerability, sensitive populations, genetic polymorphisms, dioxin, birth defects, Vietnam veterans., RFA, Health, Scientific Discipline, Toxics, Genetics, Epidemiology, Chemistry, pesticides, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, genetic susceptability, Biology, dioxin, sensitive populations, Vietnam veterans, spina bifida, P450 genes, exposure, human exposure, genetic polymorphisms, environmentally caused disease, human susceptibility, reproductive health, herbicides, dioxin exposure, genetic susceptibilityRelevant Websites:
http://www0.sph.uth.tmc.edu/research/va/vietnamvets/home.htmlProgress 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.