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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Verma, Mukesh
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital of Philadelphia
United States
Zip Code
Abdolahi, Amir; van Wijngaarden, Edwin; McClean, Michael D et al. (2013) A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma. Occup Environ Med 70:372-9
Bunin, Greta R; Li, Yimei; Ganguly, Arupa et al. (2013) Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation. Cancer Causes Control 24:343-55
Bunin, Greta R; Tseng, Marilyn; Li, Yimei et al. (2012) Parental diet and risk of retinoblastoma resulting from new germline RB1 mutation. Environ Mol Mutagen 53:451-61
Bunin, Greta R; Vardhanabhuti, Saran; Lin, Agueda et al. (2011) Practical and analytical aspects of using friend controls in case-control studies: experience from a case-control study of childhood cancer. Paediatr Perinat Epidemiol 25:402-12
Bunin, Greta R; Felice, Marc A; Davidson, William et al. (2011) Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation. Int J Cancer 128:2393-404
Nichols, Kim E; Houseknecht, Monisa D; Godmilow, Lynn et al. (2005) Sensitive multistep clinical molecular screening of 180 unrelated individuals with retinoblastoma detects 36 novel mutations in the RB1 gene. Hum Mutat 25:566-74