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Radiation Sensitivity and Cancer Susceptibility
The goal of this study is to identify genetic factors that affect individual susceptibility to radiation. Individual variations in radiosensitivity are inherited traits. In this project we identify radiosensitive and cancer susceptible individuals from an exposed population, then characterize susceptibility factors and identify the responsible genetic elements. Our study population is a group of more than 8,000 individuals who were exposed to total body irradiation (TBI) as part of hematopoietic stem cell transplantation (HSCT) for a hematologic malignancy at our institution. These individuals have a significantly increased risk of developing new solid cancers later in life as compared to transplant patients who do not receive TBI, and we have recently observed that these individuals are approximately 4-fold more sensitive to radiation-induced non-melanoma skin cancer than those exposed at Hiroshima and Nagasaki. We have also observed higher risks of second cancers in patients who develop pulmonary toxicity following HSCT suggesting a link between radiation sensitivity and cancer susceptibility. We are now collecting blood samples from these patients to use to identify the genetic basis of the susceptibility to radiogenic tumor formation. Specifically, we are analyzing changes in the sequence of genes involved in the repair of radiation-induced DNA genes. These studies will contribute to our understanding of the genetic basis of radiation sensitivity and cancer susceptibility, and to the development of more accurate estimates of individual and population risks from radiation exposures. Figure 1. Strategy for identifying genetic polymorphisms associated with radiation sensitivity.
This research is supported by a grant from the US Department of Energy. |
Copyright © 2004 University of Washington