PATERNAL EXPOSURE AND SPORADIC BILATERAL RETINOBLASTOMA

Summary

Principal Investigator: Greta R Bunin
Abstract: DESCRIPTION: We propose to conduct a molecular epidemiologic study of sporadic heritable retinoblastoma (RBL), a cancer of the embryonal retina that occurs in infants and young children. Our knowledge of the molecular events leading to sporadic heritable RBL and certain features of the disease together provide a unique opportunity for this study. In the proposed study, we will investigate sporadic heritable RBL in its own right and as a model for new germline mutation. Sporadic heritable RBL results from a new germline mutation in the RBL gene, which occurs on the father's gene in over 90 percent of cases. The study's major objectives are to investigate the role of paternal occupational, dietary, x-ray and tobacco exposures before the child's conception. Since the RBL gene is well characterized, we will do molecular genetic analyses to identify the mutation in all of the cases. The mutation data will be used with the exposure data to test hypotheses that ionizing radiation and older paternal age are risk factors for specific types of mutation. The study will use a matched case-control design with 250pairs. Cases will be ascertained through seven centers that treat most of the RBL patients in the U.S. and Canada. Controls will be identified by random-digit dialing and matched to cases on birth date, race, and geographic area. Telephone interviews will be conducted with parents of cases and controls. Blood samples will be obtained from cases and case parents, so that DNA can be isolated for mutation analysis. The proposed molecular epidemiologic study will provide new information about the etiology of sporadic heritable retinoblastoma. The study will also contribute to our knowledge of new germline mutation generally, about which very little is known. Sporadic heritable RBL is a childhood cancer worth studying in its own right and an ideal model for the investigation of new germline mutation.
Funding Period: 2001-04-06 - 2008-03-31
more information: NIH RePORT

Top Publications

  1. pmc Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation
    Greta R Bunin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Int J Cancer 128:2393-404. 2011
  2. ncbi Parental diet and risk of retinoblastoma resulting from new germline RB1 mutation
    Greta R Bunin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Environ Mol Mutagen 53:451-61. 2012
  3. pmc Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation
    Greta R Bunin
    Division of Oncology, Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Cancer Causes Control 24:343-55. 2013
  4. pmc A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma
    Amir Abdolahi
    Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Occup Environ Med 70:372-9. 2013
  5. pmc Practical and analytical aspects of using friend controls in case-control studies: experience from a case-control study of childhood cancer
    Greta R Bunin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, PA 19104, USA
    Paediatr Perinat Epidemiol 25:402-12. 2011
  6. ncbi Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene
    Kim E Nichols
    Division of Pediatric Oncology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Hum Mutat 25:566-74. 2005

Scientific Experts

  • Greta R Bunin
  • Amir Abdolahi
  • Arupa Ganguly
  • Kim E Nichols
  • Michael D McClean
  • Edwin van Wijngaarden
  • Joe G Allen
  • Robert F Herrick
  • Carol Shields
  • Monisa D Houseknecht
  • Lynn Godmilow
  • Anna Meadows

Detail Information

Publications6

  1. pmc Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation
    Greta R Bunin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Int J Cancer 128:2393-404. 2011
    ....
  2. ncbi Parental diet and risk of retinoblastoma resulting from new germline RB1 mutation
    Greta R Bunin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Environ Mol Mutagen 53:451-61. 2012
    ..As few human data exist on the role of diet in any condition resulting from new germ-cell mutation, additional studies will be needed to replicate or refute our findings...
  3. pmc Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation
    Greta R Bunin
    Division of Oncology, Center for Childhood Cancer Research, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Cancer Causes Control 24:343-55. 2013
    ..We conducted a case-control study to examine the role of parents' nutrient intake before their child's conception in the child's risk of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation...
  4. pmc A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma
    Amir Abdolahi
    Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Occup Environ Med 70:372-9. 2013
    ..The risk factors for sporadic (ie, non-familial) retinoblastoma remain largely unknown...
  5. pmc Practical and analytical aspects of using friend controls in case-control studies: experience from a case-control study of childhood cancer
    Greta R Bunin
    Division of Oncology and Center for Childhood Cancer Research, Children s Hospital of Philadelphia, PA 19104, USA
    Paediatr Perinat Epidemiol 25:402-12. 2011
    ..Although not ideal, friend controls were convenient, had a reasonably high response rate and provided controls closely matched on race/ethnicity, education and age...
  6. ncbi Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene
    Kim E Nichols
    Division of Pediatric Oncology, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Hum Mutat 25:566-74. 2005
    ..The absence of detectable RB1 mutations in eight bilateral cases and eight unilateral tumors suggests that alternative genetic mechanisms may underlie the development of RB in certain individuals...