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Continuation of Follow-up of DES-Exposed Cohorts

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00340600
First received: June 19, 2006
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

Diethylstilbestrol (DES), a drug first synthesized in 1938, was administered to several million pregnant women in the U.S. and Europe for the prevention of spontaneous abortion and premature delivery. In 1971, Herbst reported a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed female offspring. Animal models have demonstrated a range of DES effects on offspring exposed in utero, including reproductive dysfunction, immune system changes, behavioral and sexual abnormalities, and increases in various reproductive cancers in males and females. In the mid-1970's, several separate cohorts of DES-exposed daughters and unexposed comparison groups were followed for the occurrence of cancer, precursor lesions, and reproductive effects, but systematic follow-up of these cohorts had ceased by 1990. In 1992, Congress passed a bill (H;.R. 4178) mandating the continued follow-up of DES-exposed cohorts. The National Cancer Institute, in collaboration with five field centers, reassembled previously studied cohorts of DES-exposed and unexposed mothers, daughters and sons, and identified subjects with documented exposure status who had not been studied previously, through familial links within the cohorts. Standardized baseline questionnaires were mailed to cohort members to ascertain the risk of cancer and other disorders. Pathology reports were collected for reported cancers and preneoplastic conditions. Two separate rounds of follow up have been conducted and a third is almost complete. Patients from the Registry for Research on Hormonal Transplacental Carcinogenesis (the Registry) will be added to the follow-up effort in the third phase. The purpose of this study is to continue the follow-up, by means of mail questionnaires and medical record collection, which was begun during the first phase of the study. Concern has arisen that DES-exposed daughters may be at higher risk of breast cancer. Exposure to high levels of endogenous estrogen in utero has been hypothesized to increase the risk of breast cancer and DES is a potent estrogen. Cancer risk in the sons will also continue to be assessed, especially for increased risks of prostate cancer. Since the offspring who were exposed to DES in utero are currently reaching their late forties, when cancer rates begin to rise, it is important to continue the follow-up of these cohorts to determine if there are long-term increases in cancer risk.


Condition
Breast Cancer
Autoimmune Disease
Prostate Cancer
Ovarian Cancer
Endometrial Cancer

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Continuation of Follow-up of DES-Exposed Cohorts

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Cancer [ Time Frame: with each follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment: 12735
Study Start Date: March 1998
Detailed Description:

Diethylstilbestrol (DES), a drug first synthesized in 1938, was administered to several million pregnant women in the U.S. and Europe for the prevention of spontaneous abortion and premature delivery. In 1971, Herbst reported a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed female offspring. Animal models have demonstrated a range of DES effects on offspring exposed in utero, including reproductive dysfunction, immune system changes, behavioral and sexual abnormalities, and increases in various reproductive cancers in males and females. In the mid-1970's, several separate cohorts of DES-exposed daughters and unexposed comparison groups were followed for the occurrence of cancer, precursor lesions, and reproductive effects, but systematic follow-up of these cohorts had ceased by 1990. In 1992, Congress passed a bill (H;.R. 4178) mandating the continued follow-up of DES-exposed cohorts of mothers, daughters, sons and grandchildren. The National Cancer Institute, in collaboration with five field centers, reassembled previously studied cohorts of DES-exposed and unexposed mothers, daughters and sons, and identified subjects with documented exposure status who had not been studied previously, through familial links within the cohorts. Standardized baseline questionnaires were mailed to cohort members to ascertain the risk of cancer and other disorders. Pathology reports were collected for reported cancers and preneoplastic conditions. Three separate phases of follow up have been conducted. Patients from the Registry for Research on Hormonal Transplacental Carcinogenesis at the University of Chicago will be added to the follow-up effort and mailed the questionaire used in the third phase of follow-up. A cohort of daughters of women exposed and not exposed to DES in utero have been added to the study to assess the effects of DES on third generation women.

The purpose of this study as a whole is to continue the follow-up, by means of mailed questionnaires and medical record collection, which was begun during the first phase of the study. Concern has arisen that DES-exposed daughters may be at higher risk of breast cancer. Exposure to high levels of endogenous estrogen in utero has been hypothesized to increase the risk of breast cancer and DES is a potent estrogen. Cancer risk in the sons will also continue to be assessed, especially for increased risks of prostate cancer. Since the offspring who were exposed to DES in utero are currently reaching their late forties, when cancer rates begin to rise, it is important to continue the follow-up of these cohorts to determine if there are long-term increases in cancer risk.

We are planning to add a biospecimen collection component to the study. We propose to conduct a pilot study, nested within our ongoing combined cohort of DES-daughters, at Boston University to determine the feasibility of recruiting women participating in our study for phlebotomy and to investigate potential differences in the hormone metabolites and methylation patterns of germline DNA in 60 of these samples representing three groups of women: those exposed to high doses of DES prenatally, those exposed to low-doses of DES prenatally, and unexposed. Hormone metabolites and DNA methylation will be assessed in relation to DES exposure. Hormone metabolites will be measured at NCI s Frederick laboratory. DNA methylation will be assessed by Dr. Shuk-Mei Ho, the Jacob G. Schmidlapp Chair of the Department of Environmental Health, Director of the Center for Environmental Genetics, and Co-Leader of the Hormonal Malignancies Program in the Joint Cancer Center, at the College of Medicine in the University of Cincinnati, OH, and at Stephen Chanock s laboratory at NCI. The findings of this pilot study may have profound implications for the mechanisms by which endocrine disruption in the fetus influences human health. IRB approval of the data collection protocol has been received from Boston University.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Exposed daughters and unexposed daughters originally identified at: Baylor College of Medicine, University of Southern California (USC), Gunderson Clinic, Mayo Clinic, and Massachusetts General Hospital (MGH).

Male and female offspring of mothers who were enrolled in a clinical trial to assess the effectiveness of DES at the University of Chicago.

Offspring of mothers who were treated with DES by an infertility specialist, Dr. Herbert Horne, in the Boston area.

Offspring of DES-exposed mothers and unexposed mothers who were followed for breast cancer risk during the 1980s.

Exposed sons and unexposed sons who were originally identified and followed at the Mayo Clinic during the late1970's for the occurrence of cancer, genital abnormalities and infertility.

Subjects from the Registry for Research on Hormonal Transplacental Carcinogenesis.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00340600

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Boston University School of Public Health
Boston, Massachusetts, United States, 02118-2354
Tufts Medical Center 800 Washington St.
Boston, Massachusetts, United States, 02111
United States, New Hampshire
Darmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, Texas
The Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Rebecca Troisi, D.Sc. National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00340600     History of Changes
Other Study ID Numbers: 999998017, OH98-C-N017
Study First Received: June 19, 2006
Last Updated: November 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cancer
DES
Endocrine Disrupting Chemicals
In Utero

Additional relevant MeSH terms:
Autoimmune Diseases
Breast Neoplasms
Ovarian Neoplasms
Prostatic Neoplasms
Adnexal Diseases
Breast Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Diseases, Male
Genital Neoplasms, Female
Genital Neoplasms, Male
Gonadal Disorders
Immune System Diseases
Neoplasms
Neoplasms by Site
Ovarian Diseases
Prostatic Diseases
Skin Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on November 20, 2014