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

• 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 [ 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 [ Designated as safety issue: No ]
  
• Significant effect of specific DNA repair and CME genotypes on the risk of unilateral RB [ 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 [ 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 [ Designated as safety issue: No ]
  

OBJECTIVES:

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.