Induced Thyroid Cancer Research Articles

15 years after Chernobyl: new evidence of thyroid cancer

The Chernobyl nuclear power plant accident happened on April 26, 1986. We investigated the cause of the striking increase in frequency of thyroid cancer in children who lived within a 150 km radius of Chernobyl and who were born before and after the accident. No thyroid cancer was seen in 9472 children born in 1987-89, whereas one and 31 thyroid cancers were recorded in 2409 children born April 27, 1986, to Dec 31, 1986, and 9720 born Jan 1, 1983, to April 26, 1986, respectively. Short-lived radioactive fallout caused by the Chernobyl accident probably induced thyroid cancer in children living near Chernobyl.

Molecular changes in thyroid neoplasia.

All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.

Thyroid cancer following exposure to radioactive iodine.

The thyroid gland is one of the most sensitive organs for radiation-induced oncogenesis and the magnitude of the risk from external radiation is well understood. This is not the case for internal radiation derived from the radioiodines, a matter of practical importance because of medical use and potential accidental exposure. This article reviews current knowledge derived from the follow-up of patients receiving diagnostic or therapeutic 131I and populations exposed to radioactive fallout. The latter includes the nuclear power station accident at Chernobyl and the results of atomic bomb development and testing at Hanford, the Nevada Test Site and the Marshall Islands. The most cogent information comes from Chernobyl where an epidemic of childhood thyroid cancer has followed exposure to radioiodine that was mainly 131I. Although much has been learned from this experience about the nature of radioiodine induced thyroid cancer in young children, the reconstruction of thyroid radiation doses is too preliminary to provide accurate knowledge of the risk in comparison to that from external radiation. In the Marshall Islands, much of the exposure was from short-lived radioiodines as well as external radiation, obviating the possibility to determine the risk from 131I. Exposure to 131I in the continental United States from atomic bomb testing is expected to have caused some thyroid cancers, but only in the immediate vicinity of the Nevada Test Site has any evidence of radiation-induced thyroid neoplasms been adduced. This evidence is minimally significant statistically, and not significant for thyroid cancer per se. Medical use of radioiodine has not been observed to cause thyroid cancer but very few of the patients studied were young children, the group most sensitive to thyroid radiation. Despite these limitations, this information is sufficient to make some suggestions concerning protective measures in the case of nuclear accidents and the follow up of individuals who have been exposed.

Ras mutations are uncommon in sporadic thyroid cancer in children and young adults.

Mutations in the ras genes (H-ras, K-ras, and N-ras) occur in 10-15% of all human cancers, and commonly arise from single base substitutions at codons 12, 13, or 61. Although ras mutations have been found in adult thyroid cancers, they were absent from the two studies which examined childhood thyroid cancers. Both studies included only children with radiation induced thyroid cancer, and it remains unclear if ras mutations occur in children without radiation exposure. To answer this question, we examined archival tissue blocks from 31 children with papillary thyroid cancer (PTC) 4 with follicular thyroid cancer (FTC), 2 with medullary thyroid cancer (MTC), and 1 with lymphoma (LYM). Only 1 patient with PTC had previous radiation exposure. Genomic DNA was extracted and used for PCR amplification of the ras genes. The PCR products were analyzed by oligospecific hybridization for mutations at codons 12, 13, and 61. Two of the PTCs (6.5%) contained ras mutations. Both patients had class II disease and no history of previous radiation exposure. One patient subsequently developed bone and lung metastases. The patient with lymphoma also had a ras mutation (N-61), but ras mutations were absent from all FTC and MTC. These results suggest that ras mutations are uncommon in spontaneous childhood thyroid cancer, but occur with a frequency similar to that found in previous reports of adult differentiated thyroid cancers. The number of subjects was too small to determine if ras mutations are more common in patients with aggressive papillary thyroid cancer.

A progress report of the Marshall Islands nationwide thyroid study: an international cooperative scientific study.

The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer.