Sakai and 12 co-authors reported early 2023 that the purpose of this study was to investigate whether radiation exposure due to the nuclear accident is the cause of the higher number of thyroid cancer cases found in the pediatric TUE program in FP compared with the estimated number from the cancer registry6. More than 10 years after the GEJE, the relationship between the occurrence of thyroid cancer and thyroid equivalent dose has not been fully analyzed, for the reason that estimated individual thyroid equivalent doses based on the behavioralsurvey for the four months immediately after the GEJE conducted by FP22 have only been analyzed for about 40% of patients with thyroid cancer14.
Alternatively, effective doses above 250 mSv can be estimated based on the number of Tr formations using PB lymphocytes15. However, unlike analysis of
Dic formation, which is used to estimate dose in the acute phase after radiation exposure, analysis of Tr formation is susceptible to long-term effects such as smoking, drugs, and natural radiation. The authors' previous studies revealed an increase in Dic formations after a single CT scan17, but it was impossible to find a significant increase in Tr formations19, which theoretically are produced in about an equal ratio to Dic formations23,24, and we did not find an accumulative increase in Tr formations after three consecutive CT scans18.
The authors concluded that the reason for these findings is the influence of the above confounding factors, especially in subjects who are middle-aged or older. Conversely, the present subjects were young (mean age, approximately 20 years), and we therefore considered the effect of confounding factors to be small. If the Tr formations in the present study were caused mainly by radiation exposure, the majority might have been exposed to about 100 mSv, regardless of their history of CT examination based on the calibration curves of our 23-year-old healthy subjects16, which is too high when compared to the external exposure dose estimated from the behavioral survey25, 26.
As the authors have learned from their dose-response curves16, there are age-related differences in the Tr formation even in healthy subjects, which accordingly suggests that a dose-response curve for at least every 10 years might be necessary. Therefore, it is difficult to determine radiation exposure below 100 mSv based on the number of Tr formations.
A significant feature of the present study is that rather than performing a comparison between two groups (thyroid cancer and healthy control groups), Tr aberration frequency was compared among three groups, and included patients with benign thyroid tumors and other thyroid-related diseases other than
thyroid cancer. Initially, Tr aberration frequency was significantly higher in patients with thyroid cancer (Fig. 1), which the aiuthors suspected was due to genetic instability, as has been proposed for many cancer diseases27. In fact, the thyroid cancer found in patients in Fukushima was reported to have a different genetic abnormality to those in Chernobyl28, 29.
However, there was a significant difference in Tr aberration frequency between patients with and without a history of CT examination (Supplementary Fig. 2), and the difference was no longer statistically significant after adjusting for sex and a history of CT examination (Fig. 2B). In addition, comparison of Tr aberration frequency among only those subjects with a history of CT examination showed no significant difference (Fig. 2C).
Almost all of patients with thyroid cancer or with a benign thyroid tumors had underwent CT examination prior to surgical treatment of the thyroid gland, which was mainly CT of the neck and chest. As in the authors' previous studies17, 19, in which subjects were analyzed using the WAZA-ARI system, they estimated the effective dose 30–32 as 7.1 ± 1.3 (mean ± standard deviation) mSv (n = 8) for CT of the neck, 22.8 ± 9.4 mSv (n = 4) for CT of the chest, and 54.5 ± 7.9 mSv (n = 3) for CT from the chest to pelvis. Furthermore, the effective dose for the head using the same CT equipment as above was approximately 1.8 mSv for a standard Japanese body type of adult. Although WAZA-ARI could have been used to estimate past exposure doses based on the specific detailed of each CT scanning site, in the present study the authors did not consider differences in the number of CT examinations or CT scanning sites for the following reasons:
1) CT equipment differed between facilities;
2) some thyroid cancer and non-thyroid cancer patients, including some of the control subjects, had multiple CT examinations;
3) the body region scanned was unknown in two control subjects (Supplementary table 1);
4) effective dose of head CT, which was more frequently performed in the control subjects, is lower than those for other CT scanning sites by WAZA ARI;
and
5) estimation of radiation exposure dose below 100 mSv based on the number of Tr formation is difficult, as mentioned above.