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

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.

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