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Email, January 2, 2002 Subject: UNSCEAR 2000 Summary of Thyroid Cancer in Chernobyl Victims From: Jim Muckerheide Re the inquiry about the mortality of thyroid cancer in general and in the Chernobyl thyroid cancers: In the UNSCEAR 2000 Report, Annex J on Chernobyl, after discussing the general monitoring/registry programs, the Intro to this Section is: ******** V. LATE HEALTH EFFECTS OF THE CHERNOBYL ACCIDENT 259. The studies of late health consequences of the Chernobyl accident have focused on, but not been restricted to, thyroid cancer in children and leukaemia and other cancer in recovery operation workers and residents of contaminated areas. Many studies have been descriptive in nature, but until individual dosimetry is completed, proper controls established, and methodological requirements satisfied, the results will be difficult to interpret. Quantitative estimates and projections will certainly be very unreliable without individual and reliable dose estimates. 260. The late health effects of the Chernobyl accident are described in this Chapter. These effects include malignancies, especially thyroid cancer and leukemia, non-malignant somatic disorders, pregnancy outcome and psychological effects. The focus will be on health effects in the most contaminated areas, but possible effects in other parts of the world will also be considered. A. CANCER 1. Thyroid cancer (a) Epidemiological aspects 261. Thyroid carcinomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. Although rare, they are nevertheless one of the most common cancers in children and adolescents. Thyroid cancer is known to be more aggressive in children than in adults, but paradoxically, the prognosis is supposed to be better in children [V8]. ******** There's a lot of discussion of incidence, with a brief mention of mortality in older women, not related to Chernobyl, but from other, medical, exposures. Then there's a brief paragraph: ******** 288. Although rarely fatal, the aggressiveness of the thyroid cancers found in the Chernobyl area, which is frequently present with periglandular growth and distant metastases [E1, K11, W8], argues against the findings being entirely a result of screening. Although thyroid tumours in adults are usually tumours of relatively low malignancy, they tend to be more aggressive in children [S3], so it could be argued that the growth pattern would have led to the diagnosis of a thyroid cancer sooner or later. ******** Then starting the next Section: ******** (b) Clinical and biological aspects 292. A large proportion of the childhood thyroid cancers in Belarus and Ukraine were reported to be locally aggressive; extrathyroidal growth was seen in 48%-61% of the cases, lymph node metastases in 59%-74% and distant metastases (mainly lung) in 7%-24% [F5, P2, P6, T4, T18]. Comparisons with characteristics of tumours from other countries (France, Italy, Japan, the United Kingdom and the United States) indicate a higher percentage of extrathyroidal extension for tumours from Belarus and the Russian Federation but similar percentages of cases with metastases [N5, P2, P6, V8, Z3]. 293. In a recent pooled analysis of 540 thyroid cancers diagnosed before the age of 20 years (mean age at diagnosis, 14 years) that included nine Western centres, the average male:female ratio was 1:3.2 and the mean follow-up was 20 years [F7]. Eighty-six percent were papillary thyroid carcinomas, 79%showed evidence of lymph node metastases, 20%-60% had extracapsular invasion and 23% were diagnosed with distant metastases. In nearly all cases the presenting sign was a neck mass. Thirteen of the patients died as a consequence of the disease. ******** [This is roughly 2.5% cause-specific mortality for a mean 20 year follow-up.] ******** 295. A number of thyroid cancer cases in Belarus were treated with radioiodine at the university clinics of Essen and WŸrzburg [R23]. All 145 patients had undergone operations at the Centre for Thyroid Tumors in Minsk; lymph node metastases were found in 140 patients and distant metastases in 74 of them. The mean age at diagnosis was 12 years. Among 125 children subsequently followed, 90 were classified as in complete remission and the others had partial remissions. 296. In a study of 577 Ukrainian thyroid cancer cases diagnosed in patients less than 19 years of age [T18], histopathology was evaluated in 296 cases (123 were analysed by non-Ukrainian pathologists, who confirmed the initial diagnosis in all cases).Ninety-three percent were papillary carcinomas, and 65% were found to be of the more aggressive solid/follicular type. In 55% of cases, lymph node metastases were found, and in 17% lung metastases were found either at initial diagnosis or in later follow-up. Difference in TNM classification [H17] over time did not show a significant trend towards more advanced stages (Table 62), as could have been anticipated if radiation-associated cancers are indeed more aggressive. Cancers diagnosed in 1996 and 1997 were more likely to be locally aggressive, stage T4, but they revealed the same pattern of lymph node metastases and distant spread. The male:female ratio was found to be influenced by age at the time of diagnosis (Table 63): the ratio was 1.1:1 for those less than 5 years of age at time of diagnosis and 1:2.7 for those 1518 years. However, age at time of the accident did not seem to influence the male:female ratio (Table 63). A possible sex difference in the susceptibility of the thyroid tissue to ionizing radiation did not seem to influence the gender ratio, since age at diagnosis and not age at exposure influenced the distribution. 297. In a study in the United States of 4,296 patients previously irradiated for benign disorders, 41 childhood (mean age at diagnosis, 16 years) and 77 adult (mean age at diagnosis, 27 years) thyroid cancers were found [S4]. The childhood cancers more often presented themselves with lymph node metastases and vessel invasion but were significantly smaller in adults and found incidentally when benign nodules were operated. Of the childhood cancers, 95%were papillary carcinomas compared with 84%of the adult cancers. Thirty-nine percent of the childhood cancers relapsed compared with 16% of the adult cancers. After a mean follow-up of 19 years, there was only one death due to thyroid cancer, and this was in the adult group. ******** The report then goes in to molecular biology (again making clear that issues of cellular signaling etc. are the critical factors with no clear association of cancer with specific deletions, etc. The end of the section has 2 paragraphs: ******** (c) Summary 308. There can be no doubt about the relationship between the radioactive materials released from the Chernobyl accident and the unusually high number of thyroid cancers observed in the contaminated areas during the past 14 years. While several uncertainties must be taken into consideration, themain ones being the baseline rates used in the calculations, the influence of screening, and the short follow-up, the number of cases is still higher than anticipated based on previous data. This is probably partly a result of age at exposure, iodine deficiency, genetic predisposition, and uncertainty that surrounds the role of 131I compared with that of short-lived radioiodines. The exposure to short-lived radioiodines is entirely dependent on the distance from the release and themode of exposure, i.e. inhalation or ingestion. It was only in the Gomel region, the area closest to the Chernobyl reactor, that Astakhova et al. [A6] found a significantly increased risk of thyroid cancer. It has been suggested that the geographical distribution of thyroid cancer cases correlates better to the distribution of shorter-lived radioisotopes (e.g. 132I, 133I and135I) than to that of 131I [A7]. 309. The identification of a genomic fingerprint that shows the interaction of a specific target cell with a defined carcinogen is a highly desirable tool in molecular epidemiology. However, a specific molecular lesion is almost always missing, probably because of the large number of factors acting on tumour induction and progression. Signalling via protein tyrosine kinases has been identified as one of the most important events in cellular regulation, and rearrangements of the tyrosine kinase domain of the RET proto-oncogene have been found in thyroid cancers thought to be associated with ionizing radiation [F2, I21, K14]. However, the biological and clinical significance of RET activation remains controversial, and further studies of the molecular biology of radiation-induced thyroid cancers are needed before the carcinogenic pathway can be fully understood. 2. Leukaemia There's more, but if there's further interest I'd recommend downloading the UNSCEAR 2000 Annex J, from: http://www.unscear.org/ Go to "Reports," then "2000," then "Annex J" which is the pdf file. Also go to the "Chernobyl" link, and see the report of the follow-on June 2001 Kiev Conference responding to the countries/interests in claiming major consequences of Chernobyl for financial aid purposes. Note the attendees. ******** Many specific papers can also be found. As a footnote, I went back to pull out the following data to consider: ******** 277. In a study of Ukrainian thyroid cancer patients less than 15 years old at diagnosis, registered at the Institute of Endocrinology and Metabolism, Kiev, the thyroid cancer rate for 1986-1997 exceeded the pre-accident level by a factor of ten [T18]. A total of 343 thyroid cancers occurred in patients born between 1971 and 1986, and the thyroid cancer rate for this age cohort was 0.45 per 100,000 compared with 0.04-0.06 per 100,000 before the accident. For the slightly older group of patients 15-18 years old at diagnosis in 1986-1997, 219 cases of thyroid cancers were found, and the average incidence was three times higher than that in the group diagnosed before the accident. ******** It would seem that the 0.45 rate here, under these relatively large and instantaneous releases without protective actions, and with endemic problems of iodine deficiency, etc., this tragedy produced 1 thyroid cancer in about 220,000 children. These cancers are eminently treatable; and there is NO reported mortality. The slightly older children had about 1 case in 660,000 children. In the highest dose area I recall seeing a rate was also up about a factor of a little more than 10, to 2.5 per 100,000, or about 1 case in 40,000 children. Now, let’s consider releasing radioiodines from a water reactor accident!? Even with a “cracked containment,” there would be thousands of times less radioiodine, and people would be evacuated, and we would interdict milk and “food from the garden!” :-) There is an utterly negligible possibility of adverse consequences! Regards, Jim

[NOTE: My perspective on thyroid cancer treatment is influenced by my daughter's thyroid cancer, which initially caused one lobe of her thyroid to be removed while she was in early pregnancy with her 4th child. This was of no consequence since the thyroid function is ok with one lobe. The other lobe was found to have small lesions, so they waited until after her pregnancy to remove it. She's supposed to take thyroid hormone (usually Synthroid) regularly (but she's not very good at remembering).  I suspect her cancer is a result of poor eating habits (hates fruit and most vegetables) combined with 4 pregnancies, the last ones very close together. (Joe turns 2 later this month :-) ]

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