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Followup Care, Including Risk of Carcinogenesis
Children are particularly susceptible to the transforming effects of ionizing radiation.
This is true for children exposed to radioactive fallout, release of radioactive materials
from nuclear power plants, and external beam radiation therapy for medical conditions.
External beam radiation therapy, used for example in the treatment of Hodgkin’s disease
or CNS tumors, is associated with an increased risk of second malignancies, particularly
solid tumors arising in the radiation field. In contrast, children exposed to high levels of
radioactive fallout from nuclear weapons at Hiroshima, Nagasaki, or the Marshall Islands
testing site have increased risks of leukemia, benign and malignant thyroid neoplasms,
and breast cancer (as young women). Those exposed to lower levels of radiation or
possibly a more limited number of isotopes, such as from the Chernobyl nuclear accident,
have an increased risk of thyroid neoplasms.
Thyroid nodules and cancers are one of the most frequent late complications of ionizing
radiation. Although generally uncommon in children, they are very frequent 10–20 years
after radiation exposure. Four of the 39 children (10%) exposed after the Bravo nuclear
test in the Marshall Islands developed thyroid cancer, and the incidence of thyroid
cancers increased by 193-fold in areas contaminated by the Chernobyl nuclear accident.
In contrast, only 1 of 39 children (2.5%) developed leukemia after the Marshall Islands
nuclear test (compared with 10% incidence of thyroid cancer), and the incidence of
leukemia did not increase after the Chernobyl nuclear accident (compared with 193-fold
increase in the incidence of thyroid cancer). From these data, it is clear that children are
very susceptible to radiation-induced thyroid neoplasia. Indeed, children were found to be
10-fold more likely than adults to develop thyroid neoplasms after exposure to similar
doses of ionizing radiation. It is also clear that thyroid neoplasms are a more common late
effect from radiation exposure than are leukemias.
Although there may be quantitative differences in the risk of thyroid neoplasia after both
of these accidents (Marshall Islands Bravo test and the Chernobyl accident), this could
relate to differences in the types of radionuclides released or the doses absorbed. Exact
quantification of the doses to which these children were exposed has been difficult to
determine because many ingested contaminated milk, which would be a leading source.
Quantification of the level of contamination and the quantity of milk consumed has
proved difficult. Current studies are underway to better define the individual levels of
exposure.
These data underscore the particular susceptibility of the thyroid that arises from unique
genetic changes known as recombinant ret proto-oncogene in papillary thyroid cancer
(ret/PTC) rearrangements. These rearrangements can be induced by ionizing radiation
and are sufficient to cause thyroid cancer in experimental animals. Once induced,
ret/PTC gene rearrangements generate a chimeric gene that places the tyrosine kinase
portion of the ret proto-oncogene under the control of different gene promoters, leading
to increased and uncontrolled ret tyrosine kinase activity.
Stable iodine prophylaxis can reduce the risks of thyroid cancer after nuclear disasters or
accidents but has no effect against external beam radiation therapy because the latter does
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