Breast+Neoplasm+Radiation+Etiology Clinical Trial
Official title:
Cancer Risk in X-Ray Technologists
Researchers at the National Cancer Institute and the University of Minnesota have followed a
nationwide cohort of 146,022 radiologic technologists since 1982 (Boice 1992; Doody 1998;
Mohan 2003; Sigurdson 2003). This is one of the largest cohorts of medical radiation workers
studied to date (Yoshinaga 2003)and the only one with substantial numbers of women (73%
female), extensive covariate data, both incident and death outcomes, and estimated
occupational radiation doses. The overall study objectives are to: quantify radiation
dose-response for cancers of the breast, thyroid, and other radiogenic sites; assess cancer
risks associated with genotypic, phenotypic, or other biologically measurable factors; and
determine if genetic variation modifies radiation-related cancer risks.
More than 110,000 technologists completed at least one of three comprehensive questionnaire
surveys administered over the last 20 years and 18,500 are deceased. The First Survey was
mailed during 1984-1989 to 132,454 known living radiologic technologists, of whom 90,305
(68%) completed the survey (Boice 1992). The Second Survey was mailed during 1993-1998 to
126,628 known living technologists, of whom 90,972 (72%) completed the questionnaire
(Sigurdson2003). Both surveys included detailed questions about employment as a radiologic
technologist, family history of cancer, reproductive history, height, weight, other cancer
risk factors (such as alcohol and tobacco use), history of personal diagnostic and
therapeutic medical radiation procedures, and information on cancer and other health
outcomes. A third follow-up of this cohort was recently completed. During 2003-2005, the
Third Survey was mailed or administered by telephone to 101,694 living cohort members who had
completed at least one of the two previous surveys; 73,838 technologists (73%) completed the
survey. This questionnaire elicited information on medical outcomes to assess
radiation-related risks, detailed calendar-specific employment data to refine the
occupational ionizing radiation dose estimates, and behavioral and residential histories for
estimating lifetime ultraviolet (UV) radiation exposures.
The large number of women with estimates of cumulative radiation dose to specific organs
(e.g. breast) (Simon 2006; see Figure 7 and Table 9) offers at are opportunity to study
effects of low-dose radiation exposure on breast and thyroid cancers, the two most sensitive
organ sites for radiation carcinogenesis in women.. We are not aware of any other study
population in which both quantified radiation doses and biospecimens are available for
individuals with protracted low-dose ionizing radiation exposures. Incorporation of
assessment of the role of genetic polymorphisms and molecular variants in DNA repair and
other genetic pathways that may be functionally important in radiation carcinogenesis would
provide initial results on the possible role of genetic factors in the cancer-radiation
relationship. Because large numbers of women are exposed to ubiquitous low-dose radiation
from occupational, medical, and environmental sources, the presence of radiation-sensitive
genetic variants that influence the risk of breast and other cancers would have important
public health implications.
BACKGROUND:
The Radiation Epidemiology Branch and the University of Minnesota have followed a nationwide
cohort of 146,022 U.S. radiologic technologists (USRT) since 1982 to assess cancer and other
disease risks associated with long-term repeated low doses of ionizing radiation. The USRT
Study is the largest cohort of medical radiation workers studied to date and the only one
with substantial numbers of women, extensive covariate data, incident and fatal cancer and
other outcomes, estimates of individual historical occupational radiation doses, personal
medical radiation doses, and personal and residential solar ultraviolet radiation (UVR)
doses, and biospecimens for breast and thyroid cancer cases and comparison subjects. This
cohort is uniquely suited for addressing outstanding scientific questions about differences
in risk related to the nature of radiation exposure, specifically whether risks are the same
from a single or a few high-dose exposures (e.g. atomic bomb, radiotherapy) or from many
small exposures over time that might be mitigated by DNA repair or other mechanisms. The
nationwide distribution of the cohort, with wide-ranging UVR exposures, also offers a rare
opportunity to evaluate risks for non-melanoma skin cancer with UVR, which will be a major
focus of study during the next few years.
OBJECTIVES:
1. Assess risks of cancer and other diseases from long-term low-dose occupational and
personal medical exposures.
2. Assess risks of cancer and other diseases from occupational exposure to emerging and
evolving radiologic modalities (i.e. nuclear medicine, fluoroscopically-guided
procedures).
3. Assess risks of skin and other cancers from solar ultraviolet radiation exposures.
4. Conduct discovery of genetic determinants for thyroid cancer and rapid replication of
main genotype effects for breast cancer.
5. Evaluate gene-radiation and ionizing radiation-ultraviolet radiation interactions.
ELIGIBILITY:
All radiologic technologists certified by the American Registry of Radiologic Technologists
for at least two years during 1926-1982 were eligible for study. Excluded were technologists
who resided outside the U.S.
DESIGN:
Cohort study: The full USRT cohort consists of 146,022 radiologic technologists. The cohort
is predominantly female (73%), Caucasian (93%), and presently 67 years old on average; 83%
are living and 16% are deceased or presumed deceased. Three questionnaire surveys were
conducted during 1983-2005 to collect information on occupational, personal medical, and
personal and ambient residential ultraviolet radiation exposures, other cancer risk factors,
and cancer and other disease outcomes. More than 110,000 technologists participated in the
first and/or second surveys. The most recent follow-up (third survey) was conducted during
2003-2005 to obtain detailed work history information for improving occupational dosimetry.
Enhanced estimates of individual annual badge dose (personal dose equivalent) and radiation
absorbed doses to 12 organs and tissues (breast, thyroid, brain, red bone-marrow, lung,
heart, ovary, colon, testes, skin of extremities, skin of head and neck, and lens of eye)
were recently completed for survey participants. Linear dose-response analyses are underway
to quantify risks from protracted low-dose radiation for cancers (e.g., breast, thyroid) and
other radiation-related diseases (e.g., cardiovascular, cataracts). A fourth questionnaire
survey is under development and will collect information on cancer and other disease
outcomes, work history with nuclear medicine and fluoroscopically-guided procedures, and
other risk factors. Fourth survey outcomes will be used to assess incident cancer risks with
UVR exposure data collected on the third survey. Collection of blood or buccal cell samples
from breast and thyroid cancer cases and comparison subjects continues. Future plans include
a case-control study of basal cell carcinoma to assess risks with ultraviolet and ionizing
radiation exposure, genetic variants, and interactions.
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