Since the 1950’s it has been
observed that radiation in childhood is a risk factor for thyroid carcinoma,
however, radiation may also be related to benign nodular hyperplasias. There
are two scenarios of exposure to radiation that have been studied in relation
to thyroid cancer; nuclear fallout, such as the nuclear accident in Chernobyl, and therapeutic radiation. Most research has
been base on the radiation exposure due to nuclear fall out, however exposure
due to therapeutic radiation of the head and neck, is more common. Because of the observation that radiation was creating a great risk
for cancer, the therapeutic radiation treatments are now only used in response
to morbidity and mortality cases. Unfortunately, due to the long lag time between exposure and
thyroid disease onset, the children from the 1950s and 60s are only recently
being treated for thyroid disease.
In recent studies, rat thyrocytes
subjected to radiation were found to have clonal DNA damage. In a new study conductedby Adel Assaad, Laura Voeghtly and Jennifer L. Hunt, differences in
genetic alterations were observed between the radiation-induced and sporadic
papillary carcinoma and follicular derived carcinomas. The most commonly
studied mutations in papillary carcinomas have been the ras gene mutations and,
RET/PTC translocations, and BRAF mutations. However, after studying the
Chernobyl patients with papillary carcinoma, it was observed that the radiation-induced tumors had higher
mutational rates for ras gene mutations and the RET/PTC translocations, while
the BRAF mutations were uncommon. In another study, BRAF mutation frequencies
were also found to be low in tumors of patients with history of therapeutic
radiation in childhood. This lead to the idea that BRAF mutations are generally
uncommon in radiation induced tumors. Investigators, however, took into account
the findings that the translocations alone were likely insufficient to induce
carcinomas and that there are likely other genetic and molecular events leading
to the malignant transformation. Tumor suppressor gene mutations are likely the
missing link, however tumor suppressor gene genotype has not been well studied
in radiation-induced tumors of either of the two exposure scenarios.
PCR was also performed for 18 different genetic loci, identified from the comparative study of
the rats, using thyroids from patients with a history of radiation (30 cases: 3
chronic lymphocytic thyroiditis, 11 benign hyperplastic nodules, 7 follicular
adenomas, 2 follicular carcinomas, 7 papillary thyroid carcinomas), patients
who had recent therapeutic external beam radiation for laryngeal carcinoma (12
cases), and patients who had no radiation and underwent thyroidectomy with
laryngectomy for laryngeal carcinoma (15 cases). The reasons for the use of therapeutic radiation treatment are listed in Table 3. After a semiquantative capillary
electrophoresis analysis was performed, the frequency of allelic losses from
each group was calculated. The frequency of allelic loss from non-radiated
patients was 2.3%, while the frequency of allelic loss of patients radiated as
children was 39%. The frequency of
allelic loss was also high in patients with benign nodular diseases who were
subjected to radiation as a child.
It was clear that the growing thyroid of
children is at greater risk than that of adults for carcinomas due to radiation
exposure. Even if the transformation is not malignant, radiation could cause
other problems with the thyroid such as hyperthyroidism, thyroiditis,
autoimmune thyroiditis, and hyperplastic changes. The development of these
problems is caused by the propagation of the mutation abnormalities as the
thyroid matures.
