Genetic Mutations and Environmental Exposure in Young Patients With Retinoblastoma and in Their Parents and Young Healthy Unrelated Volunteers

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00690469
First received: June 3, 2008
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

This laboratory study is looking at genetic mutations and environmental exposure in young patients with retinoblastoma and in their parents and young healthy unrelated volunteers. Gathering information about gene mutations and environmental exposure may help doctors learn more about the causes of retinoblastoma in young patients.


Condition Intervention
Extraocular Retinoblastoma
Intraocular Retinoblastoma
Recurrent Retinoblastoma
Other: questionnaire administration
Other: laboratory biomarker analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Carcinogen Metabolism, DNA Repair, Parental Exposures and Retinoblastoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Association of the probability of having a child with bilateral retinoblastoma (RB) with the paternal genotype for selected DNA repair and carcinogen metabolizing enzymes (CME) genes [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Probability that mothers of unilateral RB cases are more likely to have specific DNA-repair gene variants than the mothers of the control group [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Significant effect of specific DNA repair and CME genotypes on the risk of unilateral RB [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Probability that the bilateral RB1 mutation subtype will vary by DNA repair or CME genotype or preconception exposures of the fathers of bilateral RB cases [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Probability that the unilateral RB1 mutation subtype will vary by DNA repair or CME genotype of the mother, of the affected child, and with gestational exposures [ Time Frame: Not Provided ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

saliva samples, blood and tumor samples if enrolled on ARET0332


Enrollment: 245
Study Start Date: June 2008
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Observational (biomarker analysis)

Participants undergo a structured telephone interview questionnaire. The parental questionnaires collect basic demographic data (including age, race, education, and income), occupational history, medical radiation exposure, diet and supplement use (for the year before pregnancy for father, during pregnancy for mother), tobacco use, and alcohol use. The mothers are also asked about residential pesticides and prior assisted reproductive technology.

Controls (parents) provide saliva samples. If a patient is also enrolled on COG-ARET0332, then the patient blood and tumor samples should be submitted. Parents of patients on this protocol should also submit a blood sample. Blood samples from the affected child, and blood and/or sputum samples from the parents may be submitted. Tumor specimens should be submitted if available.

For some patients, a RB1 mutation detection assay on DNA derived from peripheral blood is performed. If the mutation is found, the parents' DNA is also screened.

Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. To investigate the role of genotypes for carcinogen metabolizing enzymes (CME) and DNA repair proteins(DRPs) of the father of children diagnosed with retinoblastoma (RB) and his environmental exposures prior to the child's conception in the etiology of sporadic bilateral retinoblastoma.

II. To test if the prevalence of preconception environmental exposures and polymorphisms with known or predicted functional consequences in genes for CMEs and DRPs is different in fathers of children with sporadic bilateral RB compared with fathers of the control group.

III. To test if the prevalence of the father's preconception environmental exposures and his polymorphisms in CMEs and DRPs differs between subsets of cases defined by the type of mutation at the RB1 gene locus.

IV. To investigate the role of genotypes for CMEs and DRPs of the mother and child and environmental exposures after the child's conception in the etiology of sporadic unilateral RB.

V. To test if the prevalence of environmental exposures during the pregnancy and polymorphisms with known or predicted functional consequences in CMEs is different in the mothers of children with sporadic unilateral RB compared with mothers of the control group.

VI. To test if the prevalence of polymorphisms in genes for CMEs and DRPs with known or predicted functional consequences is different in the children with sporadic unilateral RB compared with controls.

VII. To test if the prevalence of gestational exposures and polymorphisms in genes for CMEs of the mother and the polymorphisms in genes for CME and DRPs in the children differs between subsets of cases defined by the type of mutation at the RB1 gene locus.

OUTLINE: This is a multicenter study.

Participants undergo a structured telephone interview questionnaire. The parental questionnaires collect basic demographic data (including age, race, education, and income), occupational history, medical radiation exposure, diet and supplement use (for the year before pregnancy for father, during pregnancy for mother), tobacco use, and alcohol use. The mothers are also asked about residential pesticides and prior assisted reproductive technology.

Controls (parents) provide saliva samples. If a patient is also enrolled on COG-ARET0332, then the patient blood and tumor samples should be submitted. Parents of patients on this protocol should also submit a blood sample. Blood samples from the affected child, and blood and/or sputum samples from the parents may be submitted. Tumor specimens should be submitted if available.

For some patients, a RB1 mutation detection assay on DNA derived from peripheral blood is performed. If the mutation is found, the parents' DNA is also screened. Blood samples undergo DNA-based sequencing analysis, single nucleotide polymorphism genotyping, quantitative Southern blot analysis, isolation of RNA and reverse transcriptase-polymerase chain reaction analysis, and loss of heterozygosity analysis.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Diagnosed with sporadic retinoblastoma (RB) on or after 07/01/2006

Criteria

Inclusion Criteria:

  • Cases must meet the following criteria:

    • Diagnosed with sporadic retinoblastoma (RB) on or after 07/01/2006

      • No familial retinoblastoma
    • Have permission of physician to contact the parents
    • Diagnosed and/or treated at a Children's Oncology Group (COG) institution or *Wills Eye Hospital
  • Controls must meet 1 of the following criteria:

    • Mother of a child with unilateral RB
    • Father of a child with bilateral RB
    • Age-matched non-blood-related child if possible
  • Must reside in the U.S. or Canada
  • Must have telephone in the home
  • Biological parent speaks English or Spanish
  • Concurrent treatment on a therapeutic trial is NOT required
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00690469

  Hide Study Locations
Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital Central California
Madera, California, United States, 93636-8762
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Florida
Nemours Children's Clinic - Jacksonville
Jacksonville, Florida, United States, 32207-8426
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Nemours Childrens Clinic - Orlando
Orlando, Florida, United States, 32806
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States, 32504
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60614
University of Illinois
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
University of Missouri-Columbia
Columbia, Missouri, United States, 65212
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
The Children's Medical Center of Dayton
Dayton, Ohio, United States, 45404
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Texas Tech University Health Science Center-Amarillo
Amarillo, Texas, United States, 79106
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78411
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Greta Bunin, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00690469     History of Changes
Other Study ID Numbers: AEPI05N1, NCI-2009-00366, COG-AEPI05N1, CDR0000588296, AEPI05N1, AEPI05N1, U10CA098543
Study First Received: June 3, 2008
Last Updated: January 30, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Retinoblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Neoplasms by Site
Eye Diseases
Retinal Diseases

ClinicalTrials.gov processed this record on August 28, 2014