Hall Book Ch 10 (Radiation Carcinogenesis) Flashcards
What are the two very different types of damage radiation can do?
First, damage due to cells being killed and removed form a tissue or organ for example, lethality from total body irradiation.
Second, effects due to cells that are not killed but are changed or mutated in some way, for example, cancer or heritable effects.
Damage due to cells being killed and removed from a tissue or organ was formerly called what and has renamed it as what?
It was called “deterministic effect” and has been renamed it as “tissue reaction.”
An effect due to cells that are not killed but are changed or mutated is called
“stochastic effect”
For stochastic effects, the dose response relationship is
linear
For tissue reaction (deterministic effect), the dose-response relationship has the shape of
threshold-sigmoid that is there is threshold in dose, after which the probability of the effect rises rapidly to 100%
If somatic cells are exposed to radiation, the probability f cancer increases with dose, probably with no threshold, but the severity of cancer is
not dose related.
A cancer induced by 1 Gy is no worse than one induced by
0.1 Gy, but of course, the probability of its induction is increased. This category of effect is called “stochastic.”
The word stochastic has given a special meaning in radiation protection but, in general, just means
random.
If the radiation damage occurs in ( ), mutations may occur that could cause deleterious effects in future generations
germ cells
Radiation can produce two quite different forms of damage.
A ( ) (formerly called a deterministic effect) results from some cells being killed and removed from a tissue or organ. Such effects have a threshold in dose, and the severity of the effect is dose related.
Radiation-induced lethality from ( ) is an example of a tissue reaction (deterministic effect).
tissue reaction, total body irradiation
A ( ) effect results when a cell is not killed by radiation but ( ) with a change or mutation. ( ) are examples of stochastic effects.
stochastic, survives, Radiation-induced carcinogenesis or heritable effects
In the case of stochastic effects, the severity of the effect is ( ) related, although the probability of it occurring increases with ( ) with no threshold.
not dose, dose
The human experience of radiation-induced carcinogenesis includes the survivors of the atomic bomb attacks on Hiroshima and Nagasaki, patients exposed to medical irradiation, and early workers exposed occupationally.
Some examples include the following:
- Leukemia and solid tumors in Japanese survivors of the atomic bomb
- Leukemia in patients irradiated for ankylosing spondylitis
- Thyroid cancer in children irradiated for benign conditions of the head and neck, such as enlarged thymus or tonsils, and children epilated for tinea capitis. Benign and malignant thyroid tumors were seen in children exposed to radioactive iodine at Chernobyl.
- Breast cancer in patients treated with x-rays for postpartum mastitis and patients fluoroscoped repeatedly during the management of tuberculosis
- Lung cancer in uranium miners
- Bone cancer in dial painters who ingested radium and patients who had
injections of radium for tuberculosis or ankylosing spondylitis
Latency refers to the time interval between ( ).
The shortest latency is for ( ), with a peak of 5 to 7 years.
For ( ), the latency may extend for 60 years or more.
irradiation and the appearance of the malignancy
leukemia
solid tumors
Regardless of the age at exposure, radiation-induced malignancies tend to
appear at the same age as spontaneous malignancies of the same type. Indeed,
for solid cancers, the excess risk is apparently more like a lifelong elevation
of the natural age-specific cancer risk.
To determine risk estimates for radiation-induced cancer from observed data
(the Japanese atomic bomb survivors), a model must be assumed because of
the following:
1. Data must be extrapolated from relatively high doses to the low doses of
public health concern.
2. Data must be projected out to a full life span because large exposed
populations, such as the A-bomb survivors, have not yet lived out their
life spans.
3. Risks must be “transferred” from the Japanese population to, for example,
a Western population with different natural cancer rates.
There are two principal risk models: The absolute risk model assumes that
radiation produces a discrete “crop” of cancers, over and above the
spontaneous level and unrelated to the spontaneous level. The relative risk
model assumes that radiation increases the spontaneous incidence by a factor.
Because the natural cancer incidence increases with age, this model predicts
excess cancers appearing late in life after irradiation.
The assessment of radiation-induced cancer risks by both the BEIR and
UNSCEAR committees is based on a time-related relative risk model. Excess
cancer deaths were assumed to depend on dose, square of the dose, age at
exposure, time since exposure, and, for some cancers, gender.
For solid tumors, the A-bomb data show that both the excess cancer incidence
and mortality are a linear function of dose up to about 2 Sv.
Leukemia data were best fitted by a linear-quadratic function of dose (i.e., an
upward curvature) so that the risk per unit of dose at 1 Sv is about 3 times
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that at 0.1 Sv.
The Japanese atomic bomb data refer to acute exposure at an HDR. A DDREF
is needed to convert risk estimates to the low dose and LDR encountered in
radiation protection. From animal studies, this is anywhere from 2 to 10. The
ICRP conservatively assumes a value of 2, whereas the BEIR VII committee
assumes a value of 1.5.
The BEIR VII committee suggests a risk estimate of excess cancer incidence
of 10.8% per sievert and excess cancer mortality of 5.4% per sievert,
including a DDREF of 1.5. These figures represent a population average,
with risks for females slightly higher than for males.
There is a marked reduction with age of the risk of both cancer incidence and
cancer mortality. Children are so much more radiosensitive than adults.
The ICRP estimates that, on average, 13 to 15 years of life are lost for each
radiation-induced cancer and that death occurs at age 68 to 70 years.
There is a clear excess of second cancers induced by radiation therapy, both in
heavily irradiated tissue and in more remote organs. This is evident if a
sufficiently large number of patients and an adequate control group are
available for study and if there is a sufficiently long follow-up for solid
tumors to manifest.
Large studies show a clear excess of second cancers after radiotherapy for
prostate cancer, carcinoma of the cervix, and Hodgkin lymphoma. An excess
has also been shown following radiation therapy for breast cancer, carcinoma
of the testes, and various childhood malignancies.
The INWORKS involved 308,297 workers from the nuclear industries of
France, the United Kingdom, and the United States, monitored for external
radiation exposures and followed for up to 60 years. The first part involved
death from leukemia and lymphoma. The ERR (2.63) is quite similar to that
for the A-bomb survivors despite the fact the latter received an acute dose.
This implies a DDREF close to unity. The second part of the study involved
the risk of mortality from all cancers excluding leukemia. The ERR for solid
cancers is larger than, but statistically compatible with, the estimate from a
mortality analysis of A-bomb survivors of the same age. The risk over the 0
to 100 mGy range is similar in magnitude to that for the entire dose range,
although less precise; again, little evidence of a DDREF.
Early radiologists who practiced prior to the 1920s showed an excess of
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malignancies. No excess is evident in radiologists in recent years. The report
that British radiologists live longer is not confirmed in later studies.
Irradiation in utero by diagnostic x-rays appears to increase the spontaneous
incidence of leukemia and childhood cancers by a factor of about 1.4. This is
a high relative risk because malignancies in children are rare, but the absolute
risk is about 6% per gray—not very different from the risk estimate
calculated for the A-bomb survivors following adult exposure.
From a study of both breast cancer patients receiving radiotherapy and the Abomb survivors, it is evident that doses of more than about 0.5 Sv can result
in an excess of cardiovascular diseases. It is estimated the lifetime risks of
major coronary events for patients who receive radiotherapy for breast cancer
(post-2004) range from 0.05% to 3.5%.
