USDOE Human Subjects Research Database, Fiscal Year 2003

University of Washington

Public Information Contact:

Dr. Jeffrey L. Schwartz
Department of Radiation Oncology
University of Washington
1959 NE Pacific, Box 356069
Seattle, WA 98195-6069

Phone: 206-598-4091
Fax: 206-598-6473
E-mail: jschwart@u.washington.edu

Institutional Review Board (IRB):

Human Subject Projects:

Number of Human Subjects projects reported: 1

UOW-00-069888

"Radiation Sensitivity and Cancer Susceptibility"

Project Identifier: UOW-00-069888

"Radiation Sensitivity and Cancer Susceptibility"

Principal Investigator: Dr. Jeffrey L. Schwartz, University of Washington

Project started in: 2000

Project Funding Information:

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$232,312.00 for: Fiscal Year 2003

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Identifier or number: 1534

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Fred Hutchinson Cancer Research Center
Most recent approval: 05/13/03
IRB approval number: 1534

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 30
Reporting period for number of human subjects: Fiscal Year 2003

Type(s) of Human Subjects Involvement:

External use of ionizing radiation on human subjects:

• Other. Explain:

Treated with radiation for cancer/bone marrow transplant.

Internal use of chemical substances (solid, liquid, or gas) on human subjects:

• Other. Explain:

Treated with chemotherapy/immunotherapy for cancer.

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using cells cultured in a laboratory.
• Using bodily materials collected specifically for this project.
• Using existing specimens or samples of bodily materials collected for another purpose.

Use of personally identifiable data from questionnaires, surveys, or epidemiological studies:

• Using existing data that were collected for other purposes or projects.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

The goal of this study is to identify genetic factors that affect individual susceptibility to low dose radiation. Our working hypothesis is that individual variations in radiosensitivity are inherited traits that define risks for radiation-induced cancer. Our approach is to 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 7,000 individuals who were exposed to total body irradiation (TBI) as part of hematopoietic stem cell transplantation (HSCT) for a hematologic malignancy, non-hematologic malignancy, or a non-malignant hematologic disorder. 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. The risks of tumor induction are dose-dependent and the tumors often develop at anatomical sites where the radiation dose is highest. Thus, they likely represent radiation-induced tumors. We have also observed higher risks of second cancers in patients who developed pulmonary toxicity following HSCT. The development of normal tissue damage such as pulmonary toxicity following radiation exposure often reflects an inherent radiation sensitivity in the exposed individual. Therefore, the higher risks of cancer development in patients who show pulmonary toxicity following TBI suggests a link between radiation sensitivity and cancer susceptibility. We propose to test this hypothesis and identify the genetic elements that underlie radiation sensitivity and susceptibility to radiation-induced cancer. Our study population represents a unique resource with which to address questions concerning the relationship between radiation sensitivity and cancer susceptibility. In addition to the clinical histories of the HSCT patients, we have normal lymphocytes collected prior to any radiation exposure for many of these individuals, and biopsies of the radiation-induced tumors. We propose to continue to expand this data base and tissue bank and add skin biopsies sampled at regular intervals post-HSCT for longitudinal in vitro studies. These studies will contribute to our understanding of the genetic contribution to radiation sensitivity and cancer susceptibility, and this information will in turn lead to more accurate estimates of individual and population risks from low dose radiation exposures.

Along with signing consents for treatment according to Fred Hutchinson Cancer Research Center (FHCRC) protocols, patients can also give consent to have blood and skin biopsies collected for investigational purposes. The risk of diverting small aliquots of peripheral blood for research purposes is negligible. Skin biopsy sites, generally on arm or back, heal within days, and leave minimal scars. The need for medical intervention as part of the acquisition of research samples is considered extremely unlikely. Documentation of informed consent is obtained at the time. Samples will only be taken from donors who give informed consent using forms approved by the FHCRC Institutional Review Board. Family history will be obtained in such a way as to protect the confidentiality of relatives of patients. Family history data are obtained using questionnaires and consent forms approved by the FHCRC Institutional Review Board. Only relative's initials will be requested on the family history form. Confidentiality of individuals is protected by referring to specimens by code number. Subjects will not be identified individually in any publication or other public presentation of the study.