ORIGINAL ARTICLE

5IZSPJE$BODFS%FUFDUJPOCZ6MUSBTPVOE"NPOH
3FTJEFOUT"HFT:FBSTBOE:PVOHFSJO'VLVTIJNB +BQBOUP
Toshihide Tsuda,a Akiko Tokinobu,b Eiji Yamamoto,c and Etsuji Suzukib
Background: After the Great East Japan Earthquake and Tsunami
in March 2011, radioactive elements were released from the Fukushima Daiichi Nuclear Power Plant. Based on prior knowledge, concern emerged about whether an increased incidence of thyroid cancer
among exposed residents would occur as a result.
Methods: After the release, Fukushima Prefecture performed ultrasound thyroid screening on all residents ages ≤18 years. The firstround of screening included 298,577 examinees, and a second roundbegan in April 2014. We analyzed the prefecture results from the firstand second round up to December 31, 2014, in comparison with theJapanese annual incidence and the incidence within a reference areain Fukushima Prefecture.
Results: The highest incidence rate ratio, using a latency period of
4 years, was observed in the central middle district of the prefecture compared with the Japanese annual incidence (incidence rate
ratio = 50; 95% confidence interval [CI] = 25, 90). The prevalenceof thyroid cancer was 605 per million examinees (95% CI = 302,
1,082) and the prevalence odds ratio compared with the reference
district in Fukushima Prefecture was 2.6 (95% CI = 0.99, 7.0). In
the second screening round, even under the assumption that the restof examinees were disease free, an incidence rate ratio of 12 hasalready been observed (95% CI = 5.1, 23).
Editor's Note: A commentary on this article appears on page xxx.
Submitted 25 January 2015; accepted 10 August 2015.
From the aDepartment of Human Ecology, Graduate School of Environmental
and Life Science, Okayama University, Okayama, Japan; bDepartment of
Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; and cDepartment
of Information Science, Faculty of Informatics, Okayama University of
Science, Okayama, Japan.
Presented earlier aspects of this research at conferences of the International Society for Environmental Epidemiology in Basel (2013) and Seattle (2014).
The authors report no conflicts of interest.
Supplemental digital content is available through direct URL citationsin the HTML and PDF versions of this article (www.epidem.com).
This content is not peer-reviewed or copy-edited; it is the sole responsibility of the authors.
Correspondence: Toshihide Tsuda, Department of Human Ecology, Graduate
School of Environmental and Life Science, Okayama University, 3-1-1
Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan. E-mail: tsudatos@
md.okayama-u.ac.jp.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an
open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where itis permissible to download and share the work provided it is properly cited. The
work cannot be changed in any way or used commercially.
ISSN: 1044-3983/15/XXXXX-0000
DOI: 10.1097/EDE.0000000000000385

Epidemiology t 7PMVNF99 /VNCFS999 999

Conclusions: An excess of thyroid cancer has been detected byultrasound among children and adolescents in Fukushima Prefecture within 4 years of the release, and is unlikely to be explained by ascreening surge.
(Epidemiology 2015;XX: 00–00)

T

he Fukushima Daiichi Nuclear Power Plant released radioactive elements after the Great East Japan Earthquake andTsunami on March 11, 2011. As the wind shifted direction overtime, 131I, 134Cs, and 137Cs, in addition to other radionuclides, werereleased to both the northwest and the south of the plant.1 The relative amounts of radioactive material released were estimated to be
9.1% 131I, 17.5% 137Cs, and 38.5% 134Cs. Compared with Chernobyl where one reactor melted down, at Fukushima three reactors melted down.2 Radiation released into the atmosphere fromthe Fukushima accident was estimated to be approximately 900
petabecquerel (131I: 500 petabecquerel, 137Cs: 10 petabecquerel).
The radiologic equivalence to 131I International Nuclear Event
Scale was approximately one-sixth of the 5,200 petabecquerel
calculated to have been released by the Chernobyl accident.3
In its health risk assessment, the World Health Organization predicted that an excess of thyroid cancer cases would
result from radiation-exposed children based on a preliminary dose assessment.4,5 When the World Health Organization
reported a preliminary dose estimation in 2012, it estimatedthe mean population dose for the more-affected locations
within Fukushima Prefecture (excluding areas less than 20 km
from the plant, which were immediately evacuated4), the lessaffected remainder of Fukushima Prefecture, neighboring
Japanese prefectures, the rest of Japan, neighboring countries,
and the rest of the world.4 A map of the three variously exposed
areas within Fukushima Prefecture is shown in Figure.
The World Health Organization estimated the thyroid
equivalent doses in 2011 to be 100–200 millisieverts (mSv) in
the more affected areas and 10–100 mSv in the rest of Fukushima Prefecture as delivered by inhalation, external exposure
from ground shine, and ingestion.4 In the most contaminatedareas just outside 20 km from the plant, the proportion of exposure by inhalation was the highest among all estimated radiation
doses to the thyroid, ground shine was the second highest, andXXXFQJEFNDPN ] 1

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Epidemiology t 7PMVNF99 /VNCFS999 999

Tsuda et al.

FIGURE. .BQ PG 'VLVTIJNB 1SFGFDUVSF
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ingestion was the lowest. The report indicated that the proportion of exposure via ground shine increased as time advanced.
Aside from the screening in Fukushima Prefecture that is
the subject of this study, Watanobe et al.6 conducted a screening
exercise from 2012 to 2013 including thyroid ultrasonography for
1,137 Fukushima residents ages 18 years and younger at the timeof the accident. No thyroid cancer was detected in this screening.
In regions of Japan other than Fukushima, the Japanese Ministry of Environment conducted thyroid screening of 4,365 children and adolescents ages 3–18 years living in three prefectures(Aomori, Yamanashi, and Nagasaki) using ultrasound in the 2012fiscal year7; one thyroid cancer case was detected.8 We summarize previously collected data on thyroid screening including thatin Chernobyl in the eTable 1 (http://links.lww.com/EDE/A968).
Three years and 10 months after the accident, the main
objective of this study was to establish accurate and quantitative estimates from the Fukushima experience and to plan for
the future public health needs of the population.

METHODS
Exposure Estimation
Exposure information on 131I from the Fukushima
release has been uncertain because of the 8-day half-life of131
I and the destruction of monitoring sites as a result of theevent. To explain differences in the regional distributions ofestimated internal exposures (through inhalation and ingestion, for example, of 131I) and external exposures (for example
134
Cs and 137Cs), Torii et al.1 suggested that the differenceswere due to substantial 131I concentrations in the south area of
2 ] XXXFQJEFNDPN

the plant, together with exposure differences between radioactive iodine and the total air dose rate.
In addition to Japanese sources9–11 that were cited by theWorld Health Organization,4 Unno et al.12 reported chronological changes in 131I radioactivity levels in fallout per day
in various cities; in 131I radioactivity levels in spinach, cow’s
milk, and chicken eggs; and in tap water pollution with 131I
from March to May of 2011 in various areas of east Japan.
They did not consider radioiodine exposure through inhalation. They also measured radioiodine concentrations in breast
milk from 119 volunteer lactating women residing within 250
km of the Fukushima nuclear power plant between April 24
and May 31, 2011. Seven of 23 women who were examinedin April secreted a detectable level of 131I in their breast milk.
The National Institute of Radiological Sciences estimated equivalent doses in mothers and infants from the dataof Unno et al.,12,13 based on an acute ingestion model.14 Theseestimated doses ranged from 119 to 432 mSv among mothers
and from 330 to 1,190 mSv in their infants for those living 45 to
220 km south or southwest, including Iwaki City in the Fukushima Prefecture, Ibaragi Prefecture, and Chiba Prefecture.
However, Nagataki et al.15 reported that thyroid radiation doses in children in the evacuation and deliberate evacuation areas were estimated to be 10 mSv in 95.7% of children(maximum: 35 mSv) among 1,083 by screening and intake
scenario. The timing of evacuations from heavily contaminated areas within 20 km, and from additional contaminatedareas mainly northwest of the Fukushima plant, occurred
between March 12 and mid-June 2011.3 Many residents were
evacuated to areas within Fukushima Prefecture, especially to© 2015 Wolters Kluwer Health, Inc. All rights reserved.

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Epidemiology t 7PMVNF99 /VNCFS999 999

Thyroid Cancer Among Young People in Fukushima

the middle area, defined in “Subjects and Their Screening,”
for reasons of convenience. Therefore, such evacuees continued to be exposed much like the residents in the middle area.
Although several studies independently estimated dose–
response relationships between radioiodine and thyroid cancer
incidence in Chernobyl,16–18 precise doses for cumulative radiation have not yet been established. Because there is no precise
measurement of external and internal radiation exposure in
Fukushima, we used the residential addresses of the subjects in
March 2011 categorized into each administrative district as asurrogate for individual radiation exposure measurement.

Subjects and Their Screening
The screening program for all residents born in Fukushima
Prefecture from April 2, 1992, to April 1, 2011, was plannedand conducted by the Fukushima Prefectural Government, andlabeled the “first round” hereafter.19 All residents 18 years old
and younger in March 2011 were screened by ultrasound during the 2011–2013 fiscal years: the “nearest area” in 2011; the“middle area” in 2012; and the “least contaminated area” in2013 as shown in Table 1. The Institutional Review Board of
Fukushima Medical University approved the screening using
ultrasound on September 22, 2011 (approval no. 1318; research
representative: Vice-President Masafumi Abe). Regarding theanalysis of the data described in this paper, the thyroid cancer
surveillance dataset was deidentified and publicly available, so
no further human subjects review was required.
The “nearest area” to the Fukushima plant, mostly within 50
km (47,768 subjects) was the most contaminated area, as indicatedby dark grey in Figure. This area includes the main evacuation

areas situated less than 20 km from the plant; the World HealthOrganization has not estimated doses in these areas.4
The “middle area” shown by light contrasting grays in Figure (50–80 km from the Fukushima power plant, with 161,135
residents of ages 18 years and younger in 2011) has a relatively
large population. These areas mostly correspond to the “moreaffected locations” in the World Health Organization report.4
We divided the middle area into four districts: the north middle
district, the central middle district, the Koriyama City district,and the south middle district. The central middle district had thehighest air dose rate among the four districts in the middle area.
We assigned the rest of Fukushima Prefecture (the “least
contaminated area” in the World Health Organization report;
158,784 subjects), indicated in white in Figure, to four districts:
the western least contaminated district, the southeastern least
contaminated district, the Iwaki City district, and the northeastern least contaminated district. The first three of these mostly
correspond to less affected locations in the World Health Organization report.4
Therefore, we divided Fukushima Prefecture into nine
districts (Figure). The residence of each subject in March 2011
was used to assign membership to the districts. Information
about major cities in each district was indicated in an online
data table including outdoor air dose rates from about noon on
March 30, 2011, which was summarized in eTable 2 (http://links.lww.com/EDE/A968).11 Subjects in areas with higher
air dose rate levels were screened earlier. The rank order ofthe screening was the nearest, the middle, and the least contaminated areas.19 On the other hand, the order of lengthof time from the accident to screening was the reverse: theTABLE 1. %FNPHSBQIJD%BUBPGUIF"OBMZTJT1PQVMBUJPO:FBST0MEBOE:PVOHFSPO.BSDI  /VNCFSTPG'JSTU&YBNJOFFT 1PTJUJWFTJO'JSTU&YBNJOBUJPO 4FDPOE&YBNJOFFT BOE%FUFDUFE$BODFS$BTFTJO&BDI"SFBPS%JTUSJDUVQUP
%FDFNCFS 

Areas and Districts (1) to (9)Nearest area (1) (2011 fiscal year)
Middle area (2012 fiscal year)
North middle district (2)Central middle district (3)Koriyama City district (4)South middle district (5)Least contaminated area (2013 fiscal year)
Iwaki City district (6)Southeastern least contaminated district (7)Western least contaminated district (8)Northeastern least contaminated district (9)Total

Population<19 Yearsa

1st Examinees

Positives in 1st
Examinees

2nd
Examinees

Cancer CasesN

A (A/N, %)B (B/A, %)C (C/B, %)D (No. Operated
Cases)

47,768161,135
57,212
21,05264,38318,488
158,784
62,28938,321
49,927
8,247
367,687

41,810 (88)139,339 (87)
50,618 (89)18,194 (86)54,063 (84)16,464 (89)117,428 (74)48,810 (78)29,656 (77)32,760 (66)6,202 (75)298,577 (81)221 (0.53)
988 (0.71)
312 (0.62)
115 (0.63)
458 (0.85)
103 (0.63)
1,042 (0.89)
429 (0.90)
230 (0.78)
323 (0.99)
53 (0.86)
2,251 (0.75)

199 (90)919 (93)297 (95)
111 (97)413 (90)96 (93)949 (91)401 (92)
210 (91)289 (89)
49 (93)
2,067 (92)

15 (15)b56 (50)12 (NA)
11 (NA)
25 (NA)
8 (NA)
39 (22)22 (NA)
7 (NA)
10 (NA)0 (0)110 (87)a

On March 11, 2011.
One operated case was diagnosed as a benign tumor by histology, but the case was assessed as cancer in this study according to cytology results.
NA indicates not available.
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Epidemiology t 7PMVNF99 /VNCFS999 999

Tsuda et al.

least contaminated, the middle, and the nearest. This resultsin underestimation of the prevalence odds ratios (PORs) byinterarea comparison when a district in the least contaminatedarea was used as a reference. Within the middle and least contaminated areas, the rough screening order for the first roundwas north middle and central middle, south middle, Koriyama
City, northeastern least contaminated, Iwaki City and southeastern least contaminated, and western least contaminateddistricts. Therefore, even within the same area, almost 1 year
passed between screening of the first screened and the lastscreened districts. Results from the first round of screening
were released approximately every 3 months.
The second round of screening began in April 2014,
with the addition of all residents born in Fukushima Prefecturefrom April 2, 2011, to April 1, 2012.20 The screening (“second
round” hereafter) will be completed in March 2016; the nearest and the middle areas were screened in the first fiscal year
and the rest will be screened in the second fiscal year. Within
2 years, the second round will cover all residents 18 years old
and younger, including those who were in utero in 2011.
Subjects with positive findings received a secondary
examination, and if necessary, underwent fine needle aspiration.19 When cancer cells were detected, the patient was followed and operated on at an appropriate time. The excised
thyroid tissue was examined histologically. Explanations
about medical decisions, such as timing of fine needle aspiration and surgery, were not made publicly available by theprefecture. In addition to the progressive course of the disease,a patient’s school schedule was also considered in the timingof procedures because of the need for hospitalization. Basedon information from Fukushima Prefecture, most fine needle
aspirations and surgeries were performed by doctors from
Fukushima Medical University.

Analysis
We defined thyroid cancer cases detected by fine needle
aspiration cytology in the secondary examination as cases of“thyroid cancer” because the number of cancer cases operated in individual cities and towns was not released by theprefecture. Among 87 cases operated, 86 cases (99%) wereconfirmed as malignancies by histological examination.
We made two comparisons of thyroid cancer occurrence: one internal and one external. For the internal
comparison, we used the southeastern least contaminateddistrict as a reference, and estimated PORs and 95% confidence intervals (CIs) for thyroid cancer in the remaining
eight districts. For the external comparison, we used theJapanese mean annual incidence rate estimates for thyroid
cancer among persons ages 19 years old and younger (i.e.,
two per 1,000,000) and 5–24 years old (6.5 per 1,000,000)
from 2001 to 2008 reported by the Japanese National Cancer Center,21 then employed three per 1,000,000 as the reference incidence and estimated incidence rate ratios (IRRs)
and 95% CIs in the nine districts. In doing so, we divided
4 ] XXXFQJEFNDPN

the prevalence by the latent duration of disease.22 Note that“latent duration” denotes the time from the date when thyroid cancer became detectable by screening and cytology to
the date when it could be diagnosed in clinical settings without screening or the date of operation. Here, we assumed
4 years for a latent duration of childhood thyroid cancer,
corresponding to the time between the Fukushima accident
and thyroid cancer detection, for which the maximum duration was 3 years and 10 months.
We calculated 95% CIs for the POR using the maximum
likelihood odds ratio with mid-P using StatCalc in Epi Info 7
and for IRR based on the Poisson distribution indicated in the
Geigy scientific tables.23

RESULTS
Table 1 shows the number of subjects in the first round ofscreening, those actually screened (“1st examinees”), those who
screened positive as indicated by referral to the secondary examination, those who actually underwent the secondary examination(“2nd examinees”), detected thyroid cancer cases by cytology,
and cancer cases as indicated by the number of surgeries.
Among 367,687 residents 18 years old and younger
in 2011, 298,577 (81%) underwent the first round screening
by the end of December 2014. The proportion of residents
who underwent screening decreased year by year: 88% in
the 2011 fiscal year; 87% in the 2012 fiscal year; and 74%
in the 2013 fiscal year. This trend was mainly induced bya lower proportion of 16- to 18-year-old examinees in theleast contaminated districts, which were screened last. Proportions of examinees among subjects in the 16–18 years
old stratum were 74% in the nearest, 63% in the middle, and
34% in the least contaminated areas. In Japanese society,residents 18 years and older tend to leave their hometown
for work or study, so some members of this group at thetime of the accident had already left by the time the screening program reached their districts.
Among 2,251 ultrasound screen-positive cases by theend of December 2014, 2,067 cases were examined in secondary examinations, which detected 110 thyroid cancer
cases, as indicated by the presence of cancer cells by cytology after fine needle aspiration. Among the 110 cases, 87
cases were operated by the end of December 2014: 86 cases
were histologically confirmed (83 papillary carcinomas andthree poorly differentiated carcinomas), and one case wasdiagnosed as a benign tumor.
Table 2 shows the results of both the internal and external comparisons. The results of external comparisons indicate
an excess in IRRs in all three areas, except for the northeastern least contaminated district in which no thyroid cancer
cases were detected.
When based on histologically confirmed cases that wereoperated on, the IRRs for external comparisons using a latent
duration of 4 years were 28 (95% CI = 15, 47) in the nearest
area (excluding one benign case), 30 (95% CI = 22, 39) in the© 2015 Wolters Kluwer Health, Inc. All rights reserved.

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Epidemiology t 7PMVNF99 /VNCFS999 999TABLE 2.

Thyroid Cancer Among Young People in Fukushima

1SFWBMFODF 1SFWBMFODF0EET3BUJPT 103 BOE*ODJEFODF3BUF3BUJPT *33 JO&BDI%JTUSJDUVQUP%FDFNCFS 

Areas and Districts (1) to (9)Prevalence of Thyroid Cancer
Cases per 106 (95% CI)

Nearest area (1) (2011 fiscal year)
Middle area (2012 fiscal year)
North middle district (2)Central middle district (3)Koriyama City district (4)South middle district (5)Least contaminated area (2013 fiscal year)
Iwaki City district (6)Southeastern least contaminated district (7)Western least contaminated district (8)Northeastern least contaminated district (9)359 (201, 592)
402 (304, 522)
237 (123, 414)
605 (302, 1,082)462 (299, 683)
486 (210, 957)
332 (236, 454)
451 (282, 682)
236 (95, 486)
305 (146, 561)
0 (0, 595)Internal Comparison

External Comparison

POR (95% CI)

IRRa (95% CI)

1.5 (0.63, 4.0)
1.7 (0.81, 4.1)
1.0 (0.40, 2.7)
2.6 (0.99, 7.0)
2.0 (0.87, 4.9)
2.1 (0.7, 6.0)–
1.9 (0.84, 4.8)
1 (reference)
1.3 (0.49, 3.6)
0.00 (0.0, 2.6)30 (17, 49)
33 (25, 43)
20 (10, 35)
50 (25, 90)
39 (25, 57)
40 (17, 80)
28 (20, 38)
38 (24, 57)
20 (7.9, 41)
25 (12, 47)
0.00 (0.0, 50)a
The IRRs were based on diagnosis by cytology. When based on histologically confirmed cases that were operated on, the IRRs for external comparisons using a latent duration of
4 years were 28 (95% CI = 15, 47) in the nearest area (excluding one benign case), 30 (95% CI = 22, 39) in the middle area, and 16 (95% CI = 10, 24) in the least contaminated area
for which the secondary examination of cytology positive cases is incomplete.

middle area, and 16 (95% CI = 10, 24) in the least contaminated area for which the secondary examination of cytologypositive cases is incomplete.
The highest IRR in the external comparisons wasobserved in the central middle district of the prefecture, 50 to
60 km west from the Fukushima power plant, where residents
were not evacuated (IRR based on positive cytology was 50;
95% CI = 25, 90). Prevalence in the district was 605 cases per
million examinees (95% CI = 302, 1,082), and the POR compared with the southeastern least contaminated district was
2.6 (95% CI = 0.99, 7.0).
Although the second round of screening that began in
the 2014 fiscal year was not included in the tables, the numbers of subjects were as follows: total subjects, 218,397; actually screened, 106,068 (49%); among them, for 75,311 (71%),
it had already been decided whether the secondary examination was necessary or not; positives in the screening, 611(0.8%); examined in the secondary examination, 377 (62% of
the positives); finally diagnosed by the secondary examination, 262 (70%); examined by fine needle aspiration, 22 (8%),
and detected eight new thyroid cancer cases by cytology up to
December 31, 2014. All of the eight cancer cases (four males
and four females with ages at the accident ranging from 6 to
17 years at the time of the accident in 2011) underwent thefirst round screening. In three among the eight cases, a ≤5.0mm nodule and/or a ≤20.0-mm cyst were detected in the firstround. The one cancer case was already operated on (histological type was papillary carcinoma). Mean age of the casesin 2011 was 12.1 ± 3.4 years in the second round, whereas itwas 14.8 ± 2.6 years in the first round. Even under the assumption that the remaining 75,303 (75,311 minus 8 cancer cases)
are disease free, an excess IRR for external comparison with 3
years as a latent duration which was maximum time since thefirst round was observed (12, 95% CI = 5.1, 23).
© 2015 Wolters Kluwer Health, Inc. All rights reserved.

DISCUSSION
Although precise measurements of both external andinternal radiation exposure in Fukushima were not obtained,
in external comparison, we observed an approximately 30-foldincrease in the number of thyroid cancer cases among children
and adolescents using the area/district of residence to provide
a surrogate for exposure information (Table 2). In the earlyreports on excess thyroid cancer from Chernobyl, place andtime were also used as a proxy for exposure information.24–26
Excesses of thyroid cancer in the central middle district byboth external and internal comparison were observed, although
the PORs were relatively lower. The finding that southernmost
districts within the middle and the least contaminated areas
had higher IRRs than the northernmost districts was consistent
with the flow of 131I being primarily in a southern direction
from the Fukushima release.
By considering the prevalence (detected cases per
1,000,000), IRRs in Table 2, and years between the accident andscreening—4 to16 years in Chernobyl and less than 4 years inFukushima—we could infer that the incidence of thyroid cancer
in Fukushima rose more rapidly than expected based on the cumulative attributable thyroid cancer risk over 15 years as estimatedby the World Health Organization.5 The radiation burden to thethyroid in Fukushima Prefecture might have been considerably
higher than estimated,4 as suggested by other measurements.12
The variability of prevalence in Chernobyl may also result fromvariability in years between the accident and screening.
One concern is that the approximately 30-fold increase
observed in the number of thyroid cancer cases in external
comparison might be the result of a screening effect. This concern is based on the potential presence of silent thyroid cancer
among children and adolescents in the unscreened regions ofJapan. However, the magnitude of the IRRs was too large to
be explained only by this bias. Furthermore, according to the
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Tsuda et al.

data reported by Fukushima Prefecture,27 positive lymph nodemetastases were observed in 40 of 54 cases (74%) operated
at the Fukushima Medical University Hospital. This finding
indicates that cancers detected by screening were not at aparticularly early stage.
In addition, a likely underestimated but clear increase(eight cases: IRR = 12 with 3 years as a latent duration) of
thyroid cancer incidence was observed in the second roundscreening among cases who were screened and cancer free inthe first round.20 This result cannot be explained by the screening effect because most occult thyroid cancer cases would
have been harvested in the first round screening.
Another concern about attributing a causal effect of the
Fukushima accident to increased thyroid cancer incidence isthat the excess within 4 years of the accident is too soon forradiation exposure to have induced thyroid cancer. In Chernobyl, however, small excesses of thyroid cancer incidence
were observed in both Belarus and Ukraine during 1987–
1989, within 3 years after the accident in 1986.28,29 Furthermore, during 1987–1989, no screening was conducted around
Chernobyl.30 The minimum empirical induction time forthyroid cancer is 2.5 years for adults and 1 year for children,
according to the US Centers for Disease Control and Prevention.31 Therefore, we considered it possible to detect thyroid
cancer related to the accident by screening using ultrasoundeven within the 2011 fiscal year.
Several limitations of this study should be mentioned.
First, coverage of the screening program and secondary examination did not include all eligible residents of Fukushima at thetime of the 2011 accident, as indicated in Table 1. The screened
population may not be fully representative of the exposed population. The proportion of examinees among eligible persons
gradually declined in the 2012 and 2013 fiscal years, mainlyin the stratum of those age 16–18 years in 2011, and half ofthe cancer cases (55 of 110) were detected in this stratum. We
could not adjust for this decline because age- and municipality (city, town, and village)-specific number of detected cancer
cases was not reported by the prefecture. Therefore, this may
induce overestimation in internal comparisons when prevalence of the 2013 fiscal year districts was used as a reference.
Second, the effect of the length of time elapsed between
the accident and timing of screening should be consideredfurther. Using later screened areas or districts as a reference
induces further underestimation when comparing each area/
district due to different empirical induction time. We underestimated the PORs because we used the southeastern least contaminated district as a reference where the screening program
was conducted in the 2013 fiscal year. Furthermore, internal
comparisons were intrinsically underestimated compared withexternal comparisons because the reference of internal comparisons was also influenced by the exposure. In particular, among
seven cancer cases observed in the reference district (Figure),four were observed in Sukagawa City, which is usually includedin the middle area as half of the city had a high air dose rate. If
6 ] XXXFQJEFNDPN

we excluded Sukagawa City from the reference, prevalence ofthe reference decreased to 170 per million. Using a 4-year latent
duration in estimating IRRs in the external comparison in thefirst round and 3-year latent duration in the external comparison of the second round of screening might also underestimate
IRRs because they were longer than the actual durations.
Third, we employed areas and districts as a surrogate
for exposure estimation, which could have introduced nondifferential exposure misclassification that can bias the effectestimates toward the null. The known etiologic factors forthyroid cancer that are possible confounders, other than radiation, include inherited genetic alterations, which are unlikely
to explain regional excesses. There is little potential for spatialconfounding both in Japan and within Fukushima Prefecture
because the subjects in this study are all residents 18 years old
and younger, as noted below. Furthermore, before the accident, no evidence existed that natural radiation was higher inFukushima Prefecture than in the rest of Japan.
Fourth, we defined thyroid cancer cases based on positive
results of fine needle aspiration cytology. However, the proportion of histologically confirmed cases among those operated was
99%, so disease misclassification seems to be negligible.
In conclusion, among those ages 18 years and younger in2011 in Fukushima Prefecture, approximately 30-fold excesses
in external comparisons and variability in internal comparisonson thyroid cancer detection were observed in Fukushima Prefecture within as few as 4 years after the Fukushima power
plant accident. The result was unlikely to be fully explainedby the screening effect. In Chernobyl, excesses of thyroid cancer became more remarkable 4 or 5 years after the accident inBelarus and Ukraine, so the observed excess alerts us to prepare for more potential cases within a few years. Furthermore,
we could infer a possibility that exposure doses for residents
were higher than the official report or the dose estimation by
the World Health Organization,4 because the number of thyroid
cancer cases grew faster than predicted in the World HealthOrganization’s health assessment report.5
Note added in editing: Additional new data were released
from Fukushima Prefecture on May 18, 2015, and two thyroid
cancer cases from the first round of screening and seven cases
from the second round of screening were added to the resultspresented in this article. The IRR of external comparison witha 3-year latency in the second round of screening increased to13.7 (95% CI = 7.7, 23). We provide this information in theeTable 3, eTable 4, and the text of the eAppendix (http://links.
lww.com/EDE/A968).

ACKNOWLEDGMENTS
The authors are grateful to Colin L. Soskolne, PhD,
Martin Tondel, MD, PhD, Erik R. Svendsen, PhD, Gaston
Meskens, MSc, and Wael Al-Delaimy, MD, PhD, for theirthoughtful suggestions and constructive discussions on
cancer-related issues relating to the 2011 nuclear accident inFukushima, Japan, and for constructive editorial assistance© 2015 Wolters Kluwer Health, Inc. All rights reserved.

Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Epidemiology t 7PMVNF99 /VNCFS999 999

through earlier drafts of this article. The authors also thankTetsuji Imanaka, MSc, Keiji Hayashi, MD, and Okujou Iwami
MD, PhD, for providing important references.
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