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

Carcinogen Metabolism, DNA Repair, Parental Exposures and Retinoblastoma

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.

Study Overview

• Status: Completed
• Conditions: Intraocular Retinoblastoma; Recurrent Retinoblastoma; Extraocular Retinoblastoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

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.

• Study Type: Observational
• Enrollment (Actual): 234

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
• Puerto Rico
  • San Juan, Puerto Rico, 00912
    • San Jorge Children's Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Madera, California, United States, 93636-8762
      • Children's Hospital Central California
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Francisco, California, United States, 94143
      • UCSF Medical Center-Parnassus
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic-Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Orlando, Florida, United States, 32806
      • Nemours Children's Clinic - Orlando
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Hospital
    • Pensacola, Florida, United States, 32504
      • Nemours Children's Clinic - Pensacola
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
    • Tampa, Florida, United States, 33607
      • Saint Joseph's Hospital/Children's Hospital-Tampa
    • West Palm Beach, Florida, United States, 33407
      • Saint Mary's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital-Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital at Spectrum Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Columbia Regional
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Kansas City, Missouri, United States, 64108
      • The Childrens Mercy Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Research Foundation CCOP
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Childrens Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center-Amarillo
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Not Provided
Probability that mothers of unilateral RB cases are more likely to have specific DNA-repair gene variants than the mothers of the control group	Not Provided
Significant effect of specific DNA repair and CME genotypes on the risk of unilateral RB	Not Provided
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	Not Provided
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	Not Provided

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Greta Bunin, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2008
• Primary Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: June 3, 2008
• First Submitted That Met QC Criteria: June 3, 2008
• First Posted (Estimate): June 4, 2008

Study Record Updates

• Last Update Posted (Actual): October 8, 2019
• Last Update Submitted That Met QC Criteria: October 4, 2019
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma
• Other Study ID Numbers: AEPI05N1 (Other Identifier: CTEP); U10CA098543 (U.S. NIH Grant/Contract); NCI-2009-00366 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); COG-AEPI05N1; CDR0000588296