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

Intraocular Retinoblastoma Clinical Trial

Official title:

Carcinogen Metabolism, DNA Repair, Parental Exposures and Retinoblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00690469
• Other study ID #: AEPI05N1
• Secondary ID: NCI-2009-00366CO
• Status: Completed
• Start date: June 2, 2008

Study information

• Verified date: July 2018
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 234
• Est. primary completion date: September 1, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Extraocular Retinoblastoma
• Intraocular Retinoblastoma
• Recurrent Retinoblastoma
• Retinoblastoma

Intervention

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

Locations

Country	Name	City	State
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Puerto Rico	San Jorge Children's Hospital	San Juan
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center-Amarillo	Amarillo	Texas
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Columbia Regional	Columbia	Missouri
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Children's Hospital Central California	Madera	California
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	UCSF Medical Center-Parnassus	San Francisco	California
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Significant effect of specific DNA repair and CME genotypes on the risk of unilateral RB		Not Provided
Primary	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
Primary	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