Survivors of childhood cancer have an increased risk of subsequent malignancy at another site. Previous studies in the Childhood Cancer Survivor Study (CCSS) have shown that the most frequent second malignant neoplasm is basal cell carcinoma (BCC), and that the most significant risk factor for BCC is exposure to therapeutic radiation. These data contrast with incident cases of BCC in the general population, for which the key risk factors are sun exposure and skin color. While it is clear that therapeutic radiation exposure increases risk of BCC in childhood cancer survivors, many are exposed to radiation and do not develop BCC. Thus, to address this inter- individual variation, given common exposures, we hypothesize that biomarkers of genetic susceptibility to BCC as a second malignancy will differ from those reported for incident cases. Furthermore, the occurrence of BCCs in childhood cancer survivors is potentially a marker of persons with increased radiation sensitivity. In this study, we will use a candidate gene approach in a case-control comparison to explore potential biomarkers that predict risk of BCC in childhood cancer survivors. We will validate positive observations from this investigation in two follow-up studies, which examine BCC in radiation technologists and bone marrow transplant survivors, to determine the generalizability of our observations. These validation studies are outside the work scope of this grant but will be key to the application of this approach to broader populations. We have selected a candidate gene approach for this study because the strong epidemiological data implicating ionizing radiation as the primary risk factor supports a hypothesis-driven approach to candidate gene selection.

Public Health Relevance

Childhood cancer survivors have a high risk of developing basal cell carcinoma (BCC), a type of skin cancer, as a long-term side effect of radiation treatment. Some survivors may be genetically susceptible to developing BCC after receiving radiation treatment for their initial cancer. For this research project, we will develop a prediction model, using genetics and treatment history, to potentially help doctors tailor each patient's therapy to minimize radiation if the child has an innate susceptibility to radiation-induced BCC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA139275-02
Application #
7894830
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Verma, Mukesh
Project Start
2009-07-16
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$185,017
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229