FY2022 Report of Activities

Radiation Effects Research Foundation

FY2022 Report of Activities
I. Report of Major Activities
Epidemiologic data on mortality and cancer incidence from the A-bomb survivors (the Life
Span Study [LSS], the in utero study) and their children (the F1 generation studies) havelong been a primary basis for national and international estimates of the risks of cancer andother diseases from exposure to ionizing radiation. The unique importance of the LSS study
stems from the combination of its large size, wide range of exposure levels, inclusion of allages at exposure, and long, high-quality follow-up of mortality and cancer incidence.
However, the LSS is only one facet of RERF’s research activities. Clinical examinations andthe collection of biosamples in the Adult Health Study (AHS, a subsample of the LSS) andthe clinical, epidemiological and genetic studies of the children of A-bomb survivors provide
more detailed information on health conditions of interest, including radiation-related noncancer conditions, and the pathogenesis of those conditions in relation to radiation exposure,
as well as the study of heritable mutations. Our basic science groups, in collaboration withthe clinical studies and epidemiology departments, utilize the biosamples to further address
the nature and extent of genetic (both heritable and somatic) effects, and molecular changes
associated with health risks. These three components within the RERF research programprovide an integrative approach into epidemiological, clinical, biological, and mechanistic
aspects of human radiation risk. Such integrated opportunities are unique to RERF anddemand the best possible science be conducted for the benefit of the survivors and theradiation research community. As we move forward, the primary focus of RERF studies will
be on such integrated research programs through their development within the cancer,
genetic and non-cancer research clusters. An additional and essential component of ourresearch program development is the expansion of collaborations with institutions outsideof RERF both in Japan and internationally. We have recently developed in partnership with
our Board of Councilors a strategic plan emphasizing integrative approaches in our futurestudies.
1. Research Projects Examining A-bomb Survivors Health1) Radiation and Cancer:To investigate the genomic alteration of subjects who developed MDS, the whole exome
sequencing (WXS) of stored blood samples obtained from AHS subjects who developed
MDS during follow-up has been conducted for serially collected blood samples of thosesubjects before the onset of MDS. The somatic mutations were identified, and the data will
be analyzed with their clinical measurements collected through the AHS examinations. The
number of subjects is 16, and the sequence data is only for subjects who developed MDS.
Therefore, several challenges for the statistical analysis are expected in this project including
the statistical power to detect associations among variables. However, these data will provide
important information for the clonal hematopoiesis program project, and longitudinalhematopoietic measurements recently investigated in AHS such as RDW (Yoshida, Misumi,
Kusunoki, et al. British Journal of Hematology, 2020) and monocytes (Yoshida, French,
Yoshida, et al. British Journal of Hematology 2017) will be combined with this genomic
data. Along with the statistical analysis of this project, a methodological study will be
conducted for the investigation of causal relationship among longitudinal measurements ofgenomic and clinical measurements.

1[Chronic myeloid leukemia (CML) study (RP-P2-19 and RP-P1-23, Yoshida N)]
Leukemia is the only malignancy that developed shortly after the A-bomb, and it is widely
recognized that radiation exposure can induce leukemia. A study of leukemia morphologicalclassification (French-American British classification) among A-bomb survivors in 19501980 revealed that chronic myeloid leukemia (CML) most frequently developed during theperiod. CML is currently diagnosed based on the presence of the fusion gene BCR-ABL1.
We have conducted a preliminary study to assess whether formalin-fixed paraffin-embedded(FFPE) samples of 3 CML autopsy cases are available for molecular analysis. We performed
pathological analysis and extracted DNA and RNA from the unstained slides. Using theextracted DNA and RNA, we evaluated the existence of BCR-ABL1 and several genomic
mutations with a diagnostic value for hematological malignancies.
 Updated LSS mortality report (RP 1-75): Analysis of mortality risk due to atomic bombradiation among survivors is the most important in evaluation of late health effects due toexposure to atomic bomb radiation. It is because vital status and cause of death of cancer
and noncancer diseases are the most essential for evaluation of health outcomes in
epidemiology. Also information of vital status and cause of death is collected for LSS
subjects living over the whole Japan whereas information on cancer incidence is collectedfrom those living in Hiroshima and Nagasaki prefectures. International risk assessment
groups use the results of mortality risk as the primary basis for radiation-risk estimation.
Since the first LSS report was published in 1962, the results have been published periodicallyand the latest 14th report was published in 2012 for the follow-up data during 1950-2003.
Analysis for a new LSS mortality report (15th) has started using the data through 2017,
updated dose estimates, and newly available information on lifestyle and residential factors
in collaboration with the Dept. of Statistics. These analyses include investigation of doseresponse shape and radiation risk at low dose levels considering potential confounding bygeospatial factors, lifestyle factors (smoking, alcohol drinking, body mass index), someindicators representing socioeconomic status, and so on, and also variation in baseline rates.
Analysis of the same models that were used in the LSS 14 Report has been conducted forthe data extended to 2017, and the results were substantially similar to the previous report.
An integrated lifestyle dataset including information obtained from the Mail Survey 2008
has been prepared. Currently, analysis is continued using the parametric background model
used in our cancer incidence studies (Sakata R, et al.).
 Hiroshima and Nagasaki tumor/tissue registries (RPs 18-61, 29-60): Precise information ofcancer incidence and histological diagnosis of cancers is essential for radiation risk analysesof cancer. The Dept. of Epidemiology has a long history of taking care of the local systemsof national and local cancer registries and tissue registries in Hiroshima and Nagasaki,
including communication with local community, publishing annual reports, and contribution
to the related committee to establish the basic plan for cancer control in each municipality.
Also, the Department is collecting the information regarding the members of all cohorts fromthose registries. Since the legal system of national cancer registry is active for cancer cases
diagnosed in 2016 or later, the department staff has made huge efforts to utilize theinformation for studies in RERF. Although there are practical problems due to the legal
restrictions such as strict safety control standards of facilities, unlinkable anonymization in
analytical datasets, and discarding the datasets after completion of the study, the safetycontrol organizationally, physically, technically, and educationally has been completed forthe cancer information users in RERF. The infrastructure for the users in RERF has beenarranged (e.g., construction of office door locks, restriction of PC for analysis, internal web

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page for providing information on how to use the cancer incidence data for research, data
dictionary, and application to make the dataset linked with cancer incidence data). The
webinar introduced the related-law and regulations that users must follow and the new
infrastructure in RERF. However, no transfer of the data linked with the National Cancer
Registry data to foreign countries is not allowed. We must overcome this problem together
with epidemiologists and outside RERF researchers to share RERF cancer incidence data forcollaborative studies. Tissue registry in Hiroshima was ceased in 2021, so we are planning
alternative methods to collect the information of histological materials of LSS subjects withlocal pathologists in Hiroshima. Tissue registry in Nagasaki is continued and the informationis continuously available for us. Cancer incidence information of LSS through 2019 in both
Hiroshima and Nagasaki will be obtained by March 2023, from the National Cancer Registry(Sugiyama H). Population-based information has been analyzed for specific purposes tounderpin radiation risk analyses and has been submitted to the worldwide summary program,the Cancer Incidence in Five Continents, XII, by the International Agency for Research on
Cancer (IARC)/International Association of Cancer Registries (IACR). In addition, thecancer information is planned to contribute on CONCORD-4 study by the London Schoolof Hygiene & Tropical Medicine (RP-S2-17, Sugiyama H).


Since the blood specimens of approximately 25,000 A-bomb survivors who were all subjectsof the Adult Health Study, including those who developed cancer early after the A-bombings,
have been stored since the health examinations in 1958, genome analysis using these
specimens, initially for GWAS studies, will enable us to elucidate the mechanisms ofradiation-related cancer development in detail and to identify individual differences insusceptibilities to these cancers. There are complete blood samples from all AHS subjects,
and a large amount of smear samples from blood tests performed during every 2-year
examination are stored. To determine the feasibility of this approach, it is necessary toinvestigate the availability of smears prepared from trace amounts of blood specimens. In
this study, we compared the ability of the Axiom Japonica Array NEO (AJAN) and theInfinium Japanese Screening Array (IJSA) to accurately identify SNPs in DNA extracted
from smears prepared from blood specimens of six in-house volunteers. The call rates andconcordances of the SNPs in these two SNP arrays were examined and compared using
DNAs obtained from fresh-blood specimens (W-DNA) and DNAs extracted from smears
prepared from the blood specimens and amplified with the QIAGEN REPLI-g DNA
amplification kit (amplified DNA). As a result, the average call rates of W-DNA andamplified DNA for two SNP arrays were more than 99% and 96%, respectively, andconcordances were more than 93%, but IJSA showed more reliable results with an averageconcordance of 99.7%. Subsequently, a new preliminary study is being conducted using
DNA extracted from fresh and previously stored blood specimens. DNAs were extracted
from smears stored 10, 30, and 50 years ago, paper discs stored 20 years ago, and Giemsastained specimens stored 30 years ago. (Hayashi, Yoshida K, Ohishi, Yoshida N, Kato,
Sposto, Tokunaga, Ueki, and Ozasa, RP-P1-19, terminated by September 2022, and Hayashi,
Ohishi, Brenner, Kato, Cologne, Yoshida N, Hamasaki, Kodama, Tokunaga, Ueki, Matsuura,
Yoshida K, Tanabe, and Noda, RP-P2-22). PI: Hayashi.
 The purpose of this study is to investigate whether the radiation risk of colon cancer differs
between anatomical sites taking the carcinogenesis pathway of colon cancer into account.
Likelihood-based inference is conducted based on mathematical models that assume twopath-multi-stage carcinogenesis with some parameters related to radiation exposure. This isa collaboration between Dr. Misumi of RERF and Dr. Kaiser, formerly of Helmholtz

3Zentrum München, Institute of Radiation Protection (HMGU). This project has recently been
on hold due to a variety of reasons – Dr. Casteletti and Dr. Simonetti, who played leadingroles in this project, left Dr. Kaiser’s group, and due to funding considerations Dr. Kaiser
has decided to move from HMGU to another institute in January 2023 in order to continue
conducting radiation research. Dr. Kaiser has agreed to continue conducting mechanistic
modeling of the LSS data after his move. Mechanistic models developed for colon cancer
are ready for use in a simplified setting such as two-paths two-stage. Also, the R script formechanistic model has been completed and an R package msce was developed. At the Zoom
meeting in 2022, the milestones have been updated. Dr. Misumi will start investigating theR package Dr. Kaiser’s group developed and will also start analyzing the LSS data. Also,
Drs. Kaiser and Misumi will both analyze the adenoma data of Bavaria and LSS, respectively,
and will continue discussions in 2023.
2) Radiation and Non-Cancer Effects:
Ophthalmologic examinations for our cataract study using these devices were initiated in
Hiroshima and Nagasaki in collaboration with ophthalmologists in Hiroshima and Nagasaki
Universities in April 2016. Supervision for this study is made by a cataract specialist in
Kanazawa Medical University. Ophthalmologic examinations among 1048 AHS subjects
who were ≤15 years of age at the time of bombings (including 115 in utero exposed subjects)
were finished in March 2020 in Hiroshima and Nagasaki. Scoring of cataract severity using
photographed images was completed by an ophthalmologist and a statistical analysis wascompleted in collaboration with the Statistics Department.
The presence or absence of cataracts was analyzed by inverse probability weighting logistic
regression model (IPWLR) to account for possible missing data due to cataract surgery.
The results of analysis suggested that cataract prevalence was significantly associated withage, sex, city, smoking, ultraviolet, and axial length. A significant association between
radiation and posterior subcapsular cataracts was also shown. However, radiation effect on
cortical cataracts was not observed. 86% of the participants of the present study did notparticipate in the past cataract study conducted in 2000-2002. This may be one of the reasonsfor the difference between the results of the previous and current studies.
 It has been recognized since the 1960s that the heart may be damaged by substantial dosesof radiation (> 30 Gy), such as doses used during mantle radiotherapy for Hodgkin
lymphoma. With regard to lower dose radiation, epidemiological data are insufficient andbiologically plausible mechanisms are lacking, although there are several theories which
may be applied to lower dose exposure, including microvasculature effects, oxidation,
inflammation, and mutation theories. Previous results from the LSS and AHS indicated theassociation between radiation exposure and CVD mortality or incidence, but the diversity of
disease subtypes and confounding risk factors related to CVD risk complicate the estimatesof radiation effects. We have conducted studies the objectives of which are to examine indetail the association between radiation exposure and atherosclerosis, heart disease, chronic
kidney disease (CKD), stroke, and myocardial infarction.
 [Atherosclerosis study, Part 1(RP7-09, Nakamizo T)]
Past studies have reported an association between radiation exposure and cardiovasculardisease mortality/morbidity. Although the mechanism is unclear, a plausible one is radiationinduced atherosclerosis. To examine the association between radiation and atherosclerosis,
we measured a comprehensive set of indicators of atherosclerosis including ankle-brachial

4index, carotid intima-media thickness, augmentation index, central systolic blood pressure,brachial-ankle pulse wave velocity, upstroke time, and aortic calcification evaluated fromchest and lumbar X-rays among 3,775 AHS participants in 2010-2014. Data were analyzed
by structural equation modeling with latent variables representing main atherosclerotic
pathologies: 1) arterial stiffness, 2) aortic calcification, and 3) plaque.
Aortic calcification and plaque were linearly associated with radiation, but arterial stiffness
was not related to radiation. The association was not so strong—comparable to about 2 yearsof aging per Gray of radiation exposure. The results of this cross-sectional study suggest apossible causative role of radiation on atherosclerosis, which should be confirmed by future
longitudinal studies. A paper on the results has been published (Eur J Epidemiol, 2021; 36).
 [Atherosclerosis study, Part 2 (RP2-11, Nakamizo T)]
A recent study (RP 7-09) suggested a relationship with subclinical atherosclerosis. The
mechanism is, however, unclear. In addition to potential involvement of inflammation to beinvestigated in the Clonal Hematopoiesis Program Project, we will investigate disturbancein vascular repair driven by the proliferation and differentiation of vascular (mesenchymal)
stem/progenitor cells. This is a cross-sectional study among about 2,000 AHS subjects in
Hiroshima. We have measured several multi-functional cytokines involved in the injuryrepair system such as osteopontin, osteoprotegerin, and vascular endothelial growth factor(VEGF)-A. We have assessed reliability and pre-analytical properties of the measurements,
in terms of intra- and inter-assay reproducibility (coefficient of variation: CV), storage
stability, and intra-individual variation (intraclass correlation coefficient: ICC).
 [Program project: Clonal hematopoiesis and inflammatory phenotypes potentially related
to atherosclerosis risk in atomic-bomb survivors (Yoshida K, PI), project 2 (Nakamizo T)]
Previous studies in A-bomb survivors suggest a relationship between radiation exposure andatherosclerotic diseases and inflammation. Recent evidence in studies in not involving
radiation exposure suggests that clonal hematopoiesis (CH) can cause chronic inflammation
leading to atherosclerotic diseases. To evaluate the hypothesis that CH caused by irradiation
to hematopoietic stem cells is a cause of chronic inflammation and subsequentatherosclerosis in A-bomb survivors, we are initiating a study that analyzes stored AHS
datasets relating hematological profiles with inflammatory and atherosclerotic indicators.
The relevant data has been extracted from the RERF database.
 Clonal hematopoiesis (CH), potentially associated with radiation exposure and increased
risks of inflammatory diseases, is of substantial interest to the scientific community. To
develop strategies for assessments of CH linking to radiation-associated noncancer diseases,
specifically arteriosclerosis as a part of CH program project, we conducted preliminary
experiments to establish one or more mouse models that can test the hypothesis that CH in
irradiated mice is involved in pro-inflammatory phenotypes and can promote atherosclerosis
formation. Preliminary mouse experiments ensured an extremely high prevalence of CH in
3-Gy whole-body irradiated mice, and CH in each of the irradiated mice contained multiple
clones that expanded to collectively comprise 60-80% of a whole population of bone marrow
nuclear cells, suggesting that high-dose radiation can induce massive hematopoietic cell
generation and proliferation from a tiny number of stem/progenitor cells. We also examinedlongitudinal trajectories of CH mutations in irradiated mice by using longitudinally-collectedblood cells. The blood of irradiated mice exhibited elevated levels of both pro-inflammatory
myeloid cells and red blood cell distribution width (RDW), which is often observed in humanpopulations having CH. These preliminary study results have been published in Scientific5Reports (2022). To assess a feasibility study to examine CH and atherosclerosis formationin LDLR-knockout mouse model, we have initiated a preliminary experiment assessing
clonal hematopoietic cell populations in the bone marrow, the peripheral blood, and the aortaof LDLR-knockout mice irradiated with 3 Gy and fed with a high-fat diet (Yoshida,
Kusunoki et al., CR155). PI; Yoshida. Scientific Reports 12: 17276 (2022) doi:
10.1038/s41598-022-21621-6
 In this study of the reliability and stability over long-term storage and inter-individual
variation of assays for cytokines, Dr. Cologne employed linear random effects models toassess reliability via coefficients of variation (CV), intra-class correlations (ICC), and rateof decay over time. This work has resulted in the draft manuscript: Nakamizo T, Cologne
JB, Kishi T, Takahashi T, Inoue M, Ryukaku H, Hayashi T, Kusunoki Y, Fujiwara S, Ohishi
W. Reliability, stability during long-term storage, and intra-individual fluctuation of theserum levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, andinterleukin-17A. [Target Journal - TBD]. 2022; In Development. [RP 2-11] [Ahs]3) Genetic Effects of Radiation: The most important research initiative in the MBS genetics program and for RERF in generalis the whole genome sequencing (WGS) study focusing on human trios consisting of atomic
bomb survivors and their offspring. This is a major part of the institutional-wide F1 umbrella
program. In FY2022, we held meetings with external collaborators, developed the scientificresearch protocol that has been approved following external review. These studies will be
conducted in collaboration with Dr Stephen Chanock (US NCI) and Dr Nakagawa at RIKEN.
Mutation analysis will be performed on an external cloud server and an on-premise server,
and our external collaborators will be able to perform analysis on the cloud server, but will
not be able to download the data, assuring the protection of subjects’ genome information.
In addition, the correlation analysis between genome data, epidemiological data, and clinicaldata of the subjects will be performed only within RERF so that personal information willbe thoroughly managed. One of the most important challenges in this WGS research has
been obtaining social consensus and addressing ethical issues. On this point, we hosted an
ELSI International Workshop last year, and this year, we have held an external advisorycommittee on the trio-WGS research in Hiroshima and Nagasaki which included survivors
and F1s. The ethical procedural part of the research plan reflecting their comment has been
included in our protocol which is currently under review by the IRB. When approved, weplan to obtain informed consent from the subjects as soon as possible and conduct the
research. Uchimura, Satoh, Noda (MB) and Sposto (S) A part of CR162, PI; Uchimura.
 In 2022, Dr. Misumi conducted statistical analysis of longitudinal trajectories of mutations
identified in the WXS. We observed different characteristics in the variant allele frequency(VAF) of mutations between subjects with higher radiation dose exposure and those withlower radiation exposure. Relatively higher VAF existed a long time before the diagnosis of
MDS in higher dose subjects compared to lower dose subjects and the VAF increased near
the time at MDS diagnosis. Dr. Misumi applied multi-level linear mixed effects models to
describe the longitudinal difference of mutational clones between dose groups. Also, Dr.
Miyazaki and other collaborators are conducting whole genome sequencing (WGS) for
selected subjects to investigate the mutational signature of atomic bomb survivors whodeveloped MDS. The WGS will be completed during 2023. A manuscript will be written
based on the WXS and WGS results.

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2.

Research Projects on the Health of A-bomb Survivors Children (F1)We have developed the analysis plan with Statistics Department’s FOCS Analysis Working
Group through monthly meeting to examine associations between parental radiation dose
and the development of multifactorial diseases in the F1 offspring of A-bomb survivors. The
datasets are being prepared in collaboration with Departments of Statistics andEpidemiology.

[Pathogenesis of Myelodysplastic Syndrome (MDS) (RP1-17, Miyazaki Y and ImaizumiM)] This project has been developed in collaboration with the Nagasaki University and the
Kyoto University. Radiation is one of the causes of the development of hematologicalmalignancies. A-bomb survivors have a high risk of hematological malignancies, even 50
years after exposure, such as acute myeloid leukemia (AML) and MDS. Recent genome
analyses of these diseases have demonstrated that most of samples contain several genemutations, and that these mutations might be found before clinical diagnosis. We
hypothesize that a hematopoietic progenitor or stem cell with a small number of genemutation acquires additional gene mutations over time (more than several years) and causes
hematological malignancies and that ionizing radiation increases the chance of such genemutations occurring. We are conducting a study to detect mutations in serially stored blood
samples of AHS participants who developed MDS using next-generation genome analysis
technology. Objectives are to determine dynamics of mutated clones before clinicaldiagnosis of MDS and to explore how it differs by exposed radiation dose. This study willanswer the very important question about how radiation-induced myeloid malignancies
develop, which has never been tested.
Whole exome sequencing of blood samples serially collected before and after MDS
diagnosis in 17 subjects were successfully conducted with average depth of 200-fold. MDS
clones were detected 4-22 years before diagnosis and expanded during the development of
MDS. There are two patterns in clonal evolution; 1) sustained expansion of MDS clones
which had chronal-hematopoiesis related alterations (ex. DNMT3A, TET2) and 2)
remarkable clonal shift and/or rapid expansion of MDS clones which had complex
karyotypes and del11q including ATM. The former pattern was mostly observed in the lessexposed survivors (<1Gy) and the latter one was mostly observed in the high-exposed
survivors (>=1Gy). There was a difference in the trajectory of variant allele frequencies ofmutations between less-exposed and highly-exposed survivors.
Whole genome sequencing of blood samples serially collected before and after MDS
diagnosis in 9 subjects were successfully conducted with average depth of more than 100fold and the analysis is ongoing.

[Chronic myeloid leukemia (CML) study (RP-P2-19 and RP-P1-23, Yoshida N)]
Leukemia is the only malignancy that developed shortly after the A-bomb, and it is widely
recognized that radiation exposure can induce leukemia. A study of leukemia morphologicalclassification (French-American British classification) among A-bomb survivors in 19501980 revealed that chronic myeloid leukemia (CML) most frequently developed during theperiod. CML is currently diagnosed based on the presence of the fusion gene BCR-ABL1.
We have conducted a preliminary study to assess whether formalin-fixed paraffin-embedded(FFPE) samples of 3 CML autopsy cases are available for molecular analysis. We performed
pathological analysis and extracted DNA and RNA from the unstained slides. Using theextracted DNA and RNA, we evaluated the existence of BCR-ABL1 and several genomic
mutations with a diagnostic value for hematological malignancies.

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PCR /RT-PCR/droplet digital PCR (ddPCR) and pathological analyses indicated thatextracted DNA and RNA from FFPE samples are suitable for traditional molecular analysis.
Analysis of ddPCR identified BCR-ABL1 in 2 of the analyzed cases, but not in the othercase, suggesting that CML diagnosed using pathological criteria alone may result in
misdiagnosis. Review of autopsy reports suggested that all analyzed cases had
myeloproliferative neoplasms including CML because all cases showed leukocytosis in thelaboratory tests. We have also started another pilot-study related to the above to evaluate thefeasibility of using DNA and RNA extracted from old FFPE samples for high throughput
targeted sequencing.
 F1 cohort study (RPs 4-75, 18-61): Long-term studies of the F1 cohort provide a frameworkfor studying germline effects of radiation exposure and contribute important data to thelargest study of its kind. After a major paper on mortality risk assessment was published in2015, routine collection of case information is continuing. The individual doses of theparents of F1 cohort members will be updated to DS02R1 by March, 2023 and the location
at the time of bombing for the parents whose exposure status was unknown were investigatedin the basic survey materials and updated (Sakata R). As residential information is essential
for ascertainment of cancer incidence through the national cancer registry system, theinformation on participants in the F1 Offspring Clinical Study (FOCS) has been collected
and the record linkage will conduct (Sugiyama H, Kadowaki Y).
 An umbrella program project for comprehensive studies on F1, including providing
identification and availability of information of ‘trio’ members has been developed. In thisprogram, the Dept. of Epidemiology will play a leadership role in a genotype/phenotype
analyses. Dr. Noda of the Dept. of Molecular Biosciences leads this umbrella program.
 Mortality surveillance (RPs 1-75, 2-61, 4-75): This is a primary responsibility of thedepartment. Mortality follow-up for all cohorts (LSS, F1, in utero) continues on a 3-year
cycle. Mortality data are complete through 2017 and include underlying cause of death aswell as associated causes of death. Archiving has been conducted of early-period materials(scanning and digitization) including questionnaires for the major cohorts and other subjects
as part of the developing Research Resource Center (Sakata R).
 Multi-state models for disease and mortality in the F1 clinical study (FOCS)[RP4-10]
Drs. Cologne and Yamamura led a working group comprising also Dr. Sposto and Ms.
Funamoto to evaluate methods applicable to the F1/FOCS analysis, which included illnessdeath models, multi-state models (MSM) with death as an absorbing state, and issues ofinterval censoring. This group met regularly during 2020 and 2021 to study these statisticalmethods and applicable software, applying these to preliminary data from the clinical followup study of offspring of atomic-bomb survivors. Focusing initially on the intermediate statesof diabetes mellitus, hypertension, and dyslipidemia with mortality as a terminal state, Dr.
Cologne played the leading role in conducting exploratory analyses and drafting a summaryof the working group’s findings. This working group completed its work in 2021, having
investigated MSM approaches for this analysis and presenting this to Drs. Tatsukawa, Ohishi,
Hida, and other collaborators in the Clinical Studies Department. The working group
recommendations on the analytic approach were accepted. During 2022 Dr. Cologne
authored a comprehensive analytic plan for this project, which was reviewed by working
group members and collaborators in the Clinical Studies Department. The plan waspresented to and commented upon by the Scientific and Ethics Committee for the Clinical8

Study of the F1 Offspring of A-Bomb Survivors in July 2022 and was then finalized andapproved in late 2022. Dr. Cologne and Ms. Funamoto are currently finalizing the data andprocessing code necessary to perform these analyses, which should commence in Spring2023.
3. Research to Elucidate Individual Doses and Effects from the A-bomb Coordinating of Organ Dosimetry Working Group (ODWG) activities: The Department of
Statistics has continued its coordination and collaboration activities in the binational working
group that is tasked with developing an improved approach to organ dosimetry by using
existing, DS02-calculated shielded radiation fields with new response function tables
calculated from new and improved computational phantoms. Dr. Harry Cullings, former
chief of the Department of Statistics, and Ms. Sachiyo Funamoto, the member of the
Department who is primarily responsible for overseeing the technical implementation of thedosimetry system at RERF, were and are ongoing contributors to this work.
 In order to evaluate the dose dependent effects of A-bomb radiation on humans, a cytogenetic
biological dosimetry study has been conducted over several years for a subset of A-bomb
survivors in the AHS cohort. A total of 1,868 survivors (1,179 in Hiroshima and 689 in
Nagasaki) were examined using the 2-color-FISH method for detecting the frequency ofstable translocations involving chromosomes 1, 2, and 4. The dose response from FISH data
showed a wide scattering of individual translocation frequencies in both cities as we
observed in the previous solid Giemsa staining study. Differences between the two cities
remained significant but was much reduced suggesting the large city difference in the past
study was mainly due to different aberration detection rates between Hiroshima andNagasaki laboratories. The city difference was not significant when Nagasaki factory
workers were excluded from the analysis. The results suggested that radiation-shielding wasstill a significant dose-effect modifier but neither sex, city, nor smoking was significantly
associated with background rate. We published these analyses this year. Sposto et al.,Radiation Res., in press. (Kodama, Hamasaki, Cordova, Cullings, RP 8-93). PI; Kodama.


Dr. Yamamura continues here collaboration with Dr. Hida and others in the Clinical Studies
Department in a reinvestigation of the association between radiation and cataracts based on
the new DS02R1 dosimetry and rigorously standardized cataract assessment using a new
ophthalmic camera. Dr. Yamamura designed and performed the statistical analysis of therelationship between radiation exposure and prevalence of cataracts. The analysis utilized
inverse probability weighting analysis to account for informative censoring due to cataract
surgery. The manuscript for this project is now in preparation.
 This paper reports a pilot study for development of an integrated time and dose model toexplore the dynamics of gene alterations of low and high dose irradiation with transcriptome
datasets in Gene Expression Omnibus (GEO). Genes that are correlated with doses and time
were identified, and it was observed that differentially expressed (DE) genes of low and highdose exposures are involved in similar pathways. Also, there were two clusters of genes thatare either positively or negatively correlated with both dose and time based on the parametersof the model that may have long-term transcriptional alterations. The proposed model helps
to understand the long-term effects of irradiation on gene expression. This work is the subjectof a paper in development: Liu Z, Cologne JB, Amundson SA, Noda A. Candidate Biomarkers
and Long-term Transcriptional responses over low and high dose ionizing radiation. [Target

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Journal - TBD]. 2022; In Development. [No RP] [Smnos] The life span study (LSS) of A-bomb survivors provides a unique source for radiation risk
estimation. Although there are many publications out of this study, the risk estimation ischallenging and remains a focus of research. A linear dose-response model is often used forrisk estimation. Nonlinear dose-risk associations are also investigated. The computational
results of a parametric model usually depend on its model specification. Different parametricmodels may lead to inconsistent or contradictory results. Dr. Liu, with the help of Drs.
Cologne, Misumi, Nakamizo, and Ono, has proposed a deep learning model with
TensorFlow for nonlinear risk prediction with the life span cancer incidence data. This datadriven nonparametric method does not rely on any specific parametric settings, is easy to
implement, and may perform significantly better than its linear counterpart with different
metrics. This work has resulted in a paper in development: Liu Z, Nakamizo T, Cologne JB,
Misumi M, Ono S. Deep Learning for Radiation Risk Prediction of A-bomb Survivors.
[Target Journal - TBD]. 2022; In Development. [RP 1-75] [Smnos]

The work of the ODWG is approaching completion. Four papers have been published on
various aspects of the new organ dosimetry, two additional have been submitted and one
other is in development. In addition we recently discussed the issue of how best to assign
and assess uncertainty in fetal doses that arises because (a) fetal phantoms were made forseveral fixed gestational ages, but the actual gestational age may lie between that of two
phantoms; (b) true gestational age is unknown, but can only be estimated from birth date;and (c) fetal phantoms exist for three fetal positions, but fetal position changes over time andin any case is unknown. The resolution of this issue by the working group will possibly leadto an additional paper.
 With respect to dosimetry error specifically, there are a number of potential issues with thecurrent dose error corrections used at RERF that we plan to address. First, the current dose
error adjustments are based only on a classical dose error model – e.g., errors due tomisspecification of the location of the subject – but do not consider additional so-called
Berkson type error – e.g., that due to the fact that individuals at far distances, and therefore
with lower doses, do not have shielding histories, so that average transmission factors forthe corresponding shielding scenarios (inside, outside, etc.) are assigned. Second, the current
classical regression calibration dose error corrections are only applied at higher doses ( >~500 mGy in Hiroshima, > ~ 700 mGy in Nagasaki, shielded kerma). In addition, the recent
analysis of chromosome aberrations points to a systematic overestimation of doses for
Nagasaki factory workers. In light of these issues and also of the likely adoption of neworgan dose estimates, a re-evaluation of the issue of dosimetry errors is warranted.
 RERF is conducting genomics and omics studies of animal experiments and planning thoseutilizing atomic bomb survivors samples. Drs Liu and Misumi are working with a single cell
sequence data of mice experiment conducted by Dr. Yoshida and applying a standard pipeline
to investigate differential expression of genes associated with radiation exposure. Also, Dr.
Liu and other members of the Department of Statistics are collaborating with MBS and Dr.
Ono of the ITD to find out the needs of our future bioinformatics capability including thecomputational infrastructure. Moreover, massive multi-omics data are available in publicdomain. Drs Liu, Misumi, and other members of Department of Statistics are considering
exploring the potential of integrating public omics data with ongoing genetics and omics
studies at RERF.

10 The primary focus of our work on dosimetry during FY2023 is continued preparation for the
implementation of the revised organ dosimetry using updated computational phantoms, as
described above. Implementation of the revised organ dosimetry is planned for 2023.
4. Projects to Release Research Results and to Collaborate with Other Scientific
Organizations
Crucial to the mission of RERF is the dissemination of results of our studies to survivors andtheir children and to the international community. Toward that end we interact with local liaisoncouncils representing the communities of Hiroshima and Nagasaki and provide information via
public lectures and other activities. These will be described later in another section of this report.
With respect to the international community there are a number of activities. These include
seminars, workshop, participation at international scientific conferences, and international
publication of results. This year 3 seminars were held at RERF presented by national andinternational visitors to RERF and published more than 60 scientific papers.
Collaborative Research Projects
 Ongoing international collaborative research projects
In addition to the above activities the development of national and international collaborations
is essential to help disseminate results and to enhance RERF research programs. A list of
current collaborations is provided below:
a. Partnership with the University of Washington
b. Partnership with Kurume Universityc. Collaborations with the US National Cancer Instituted. Collaborations with the University of Florida
e. Collaborations with Outside Investigators:
39 Japanese Institutions
7 North American Institutions
8 European Institutions
5. Training Programs for Domestic and Overseas Specialists
1) RERF held an online epidemiological training course for radiation biologists to deepen the
biologists' understanding of RERF's epidemiological research and to promote interaction
among investigators working in radiation research institutes (August 22-23, 2022; 70
participants in total, including 40 and 30, respectively, from inside and outside RERF).
2) The Department of Epidemiology accepted a long-term internship student on the Hiroshima
University phoenix leader education program from June 6 through July 1, 2022 andprovided the student with online lectures and on-the-job training.
3) Due to the effects of COVID-19, acceptance of trainees from overseas through the Nagasaki
Association for Hibakushas’ Medical Care (NASHIM) and the like was completely
canceled; however, the training of the International Council for Health Care of Radiationexposed (HICARE) was resumed to provide online lectures.
4) There was no invitation for the MHLW-sponsored International Exchange and Research
Program in FY2022 again, so we did not recruit trainees from abroad.
5) The Department of Statistics recruited investigators who would participate in theInternational Fellowships for Research in Japan program, sponsored by the Japan Society
for the Promotion of Science (JSPS), on the RERF external website; there was a candidate

11who considered applying in 2024-2025. However, there was no applicant in FY2022 , andthe department could not apply to the relevant program.
6. Public Information Programsi) RERF public lecture series
RERF’s new public lecture series, initiated in FY2019, targets peace volunteer guides
among other such individuals, in partnership with external organizations such as theHiroshima Peace Memorial Museum. In FY2022, due to effects from the coronavirus
pandemic, this series was developed in limited numbers, involving Zoom meetings with
the Hiroshima Peace Friendship Center as well as the United Nations through theHiroshima Peace Memorial Museum.
ii) RERF Open House event
RERF held the 27th and 25th Open House event at its Hiroshima and Nagasaki laboratories.
For the second year in a row, the joint Hiroshima and Nagasaki event was held using avirtual, online format, out of consideration for the effects of the persistent coronavirus
pandemic. The total number of viewers who accessed the videos (in both English andJapanese) made specifically for the Open House events was 7,744, with the total numberof page views reaching 9,565.
iii) Strengthening of social media-related activities
In FY2022, obtaining understanding from atomic bomb survivors, the second-generationof children, local communities, and the media was positioned as the most important task
facing RERF, and social media was used to help reach that goal. RERF’s follower numbers
increased only slowly over that period, with the Facebook page reaching 862 followers asof March 31, 2023, and RERF’s English and Japanese Twitter accounts totaling 599
followers by the same time. RERF paid particular attention to the creation of videos forposting on the website, Facebook page, and YouTube channel as part of our social media
work. Videos made over the course of that fiscal year numbered 20, including those
designed for the Open House event and the initial video of a series on the genome
sequencing analysis research that RERF is planning.
iv) Promotion of public relations activities targeting media
In FY2022, RERF reinitiated gatherings and study sessions with the media to improve andstrengthen relations, but such interactions were limited to one occasion, due to thecoronavirus pandemic. Based on RERF’s continued efforts to fully engage with the media
and provide story ideas, the number of published articles featuring RERF in FY2022 totaled
105, with the plurality making up information about RERF’s relocation, as of March 31,2023.
v) Enhancement of RERF website• During FY2022, the new homepage was regularly updated with revised information andthe section on published scientific papers was enhanced for easier navigation and greater
understanding of the RERF system of paper categorization.
• During FY2022, focus was placed on conveying readily understandable research-related
and other information to the public through the utilization of more video and othermethods, particularly at the time of the Open House event.
• Starting in FY2018, when papers are published in scientific journals, new easy-to-follow

12

synopses have been posted on the public website. That synopses were further refined in
FY2022 for timely dissemination of information.
• The total number of RERF website hits, or page views, between April 1, 2022, andMarch 31, 2023, was 540,990, with the daily average being 1,482. The total number of
website visitors for the same period was 246,389, with the daily average being 675.
vi) Enhancement of online news-delivery system
In FY2022, RERF’s email magazine system, E-News, which replaced the printed Update
newsletter, was terminated and changed to a video-production system for publicizing
RERF research and other content in a more modern and visually pleasing way.
vii) School Visit Program
The RERF School Visit Program—which is an attempt to teach radiation health effects toschool children using readily understandable language—was scheduled to continue inFY2022 but had to be canceled due to the coronavirus pandemic.
viii) Facility tours
Each fiscal year, RERF tries to handle the many requests for facility tours that come in,with the aim of introducing the foundation’s history and research activities. In FY2022,
facility tours were canceled because of the coronavirus pandemic, but the Hiroshima
Laboratory was able to use outside lecture venues and RERF’s Hijiyama Hall duringcertain periods to introduce RERF and its research work to the public.
ix) Internship (work experience) project
RERF has been accepting interns, mostly those with scientific backgrounds, for some time.
In FY2022, the plan was put on hold due to the coronavirus pandemic.
x) Other public relations activities• RERF actively promoted the organization’s important scientific papers to the media via
press releases and remote press conferences.
• RERF worked to conduct training for staff to be able to provide RERF facility tours in
English, but due to its desire to protect the aging A-bomb survivor participants in RERF
studies from the coronavirus, RERF was unfortunately unable to provide sufficient
practical experience in front of visitors to such staff.
• By increasing our effort at communicating RERF’s research with the aim of improved
transparency related to RERF research and establishment of good communication withthe public, in particular A-bomb survivors, their children, and the media, the PublicAwareness Campaign (PAC) working group was formed in 2019. In FY2022, the PAC
working group members formed the core of RERF’s response to email inquiries fromthe public.
• RERF was unable to target small public groups of A-bomb survivors and their children
to come to RERF and speak with directors and staff about ABCC/RERF history andresearch results, with the aim of achieving greater understanding about RERF, due tothe coronavirus pandemic.

13

（Attachment 1）

FY2022 RERF International Collaborative Activities
I. Participation in international collaborative
activities by RERF directors and staff
members

WHO-related activity
UNSCEAR-related activity
ICRP-related activity
IAEA-related activity
Medical checkup for A-bomb
survivors residing in South
Korea-related activity
OthersII. Acceptance of visitors from overseas forbriefing and training

3 people (Hiroshima)
3 people Visitors related to HICARE
2 people Visitors related to RERF
(International Exchange
None
Research Program)None

10 people
None

Visitors related to MEXT
Visitors related to JICA

None
None

13 people

Total: 21 people(Nagasaki)
Visitors related to NASHIM
None
Total: 10 people(Hiroshima: 10 people, Nagasaki: 0 people)

I. Participation in international collaborative activities by RERF directors and staff
members (excluding participation in international scientific meetings)
In italics: Funding Organization
1. World Health Organization (WHO)-related activity (3 people)
RERF (hereinafter, all titles represent those at time of participation)(1) Kazunori Kodama, Executive Director, and Misa Imaizumi, Assistant Department
Chief of Clinical Studies (Nagasaki), participated in the 4th WHO Collaborating Centre
collaboration meeting (April 26, 2022, Online).
(2) Kazunori Kodama, Executive Director, gave a lecture entitled “Radiation Disaster
Medical System in the World—WHO’s Radiation Emergency Medical Preparedness
and Assistance Network (REMPAN) and Hiroshima” at the HICARE’s public lecture(February 2023).
2. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)-related collaborative activity (3 people)
1) National Institute of Radiological Sciences
Ritsu Sakata, Assistant Department Chief of Epidemiology, attended the UNSCEAR
domestic committee meetings (July 22, October 17, 2022, and February 27, 2023, Online).
2) RERF(1) Alina Brenner, Senior Scientist, Department of Epidemiology, attended meetings as alead writer for UNSCEAR Epidemiological studies of Radiation and Cancer (April 7,
May 9-13, June 9, September 9, December 5, 2022, January 26, and March 29, 2023,
Online, October 25-27 (IRSN, Paris in person)).
(2) Satoshi Kurisu, Senior Scientist, Department of Clinical Studies, Hiroshima, attended
the UNSCEAR CircuDis Expert Meeting (June 22, 2022, February 14, and February
28, 2023, Online).

14

3. ICRP (International Commission on Radiological Protection)-related activity (2 people)(1) Alina Brenner, Senior Scientist, Department of Epidemiology, attended meetings as amember of the ICRP Task Group 122 (Update of Detriment Calculation for Cancer)(January 4, March 6, 2023, Online).
(2) Tomoki Nakamizo, Division Chief of Radiology of the Department of Clinical Studies,
Nagasaki, attended meetings as a member of the ICRP Task Group 119 (Radiation
Effects on Diseases of the Circulatory System) (June 16, September 26 and 28, 2022,
January 31, March 29, 2023, Online).
4. IAEA (International Atomic Energy Agency)-related activity (0 person)
This activity was not done in FY2022.
5. Medical checkup for A-bomb survivors residing in South Korea-related activity (0 person)
This activity was not done in FY2022.
6. Others (13 people)(1) Eric Grant, Associate Chief of Research, attended the Workshop Jointly organized by
Task Group 121 of the International Commission on Radiological Protection (ICRP)
Committee 1 (May 31-June 2, 2022, Budapest, Hungary).
(2) Eric Grant, Associate Chief of Research, attended the 44th Scientific Assembly of the
COSPAR (July 16-24, 2022, Athens, Greece).
(3) Osamu Tanabe, Chief Scientist, gave a lecture at the 67th Annual Meeting of the Health
Physics Society (July 20, 2022).
(4) Robert Ullrich, Vice Chair, and Eric Grant, Associate Chief of Research, attended the68th Annual Meeting of the Radiation Research Society (October 16-19, 2022, Hawaii,USA).
(5) Hiromi Sugiyama, Assistant Department Chief, Department of Epidemiology, attended
a board meeting of international Association of Cancer Registries (IACR) (November
7, 2022, March 23, 2023, Online).
(6) Hiromi Sugiyama, Assistant Department Chief, Department of Epidemiology, attended
the annual meeting of international Association of Cancer Registries (IACR)(November 8-10, 2022, Online).
(7) Kazunori Kodama, Executive Director, attended the re-designation ceremony of
HICARE as a collaborating center for the International Atomic Energy Agency (IAEA)
and discussed a work plan for the next four years as the liaison officer of HICARE(November 10, 2022).
(8) Kazunori Kodama, Executive Director, participated as a lecturer in the IAEA-HICAREInternational Training Course on Advanced Radiation Therapy for Head and Neck,
Lung, and Liver Cancer (November 15, 2022).
(9) Robert Ullrich, Vice Chair, attended the NASA Human Research Program
Investigators’ Workshop (February 7-9, 2023, Houston, USA).
(10) Robert Ullrich, Vice Chair, and Eric Grant, Associate Chief of Research, chaired
sessions for the 59th Annual Meeting of the National Council on Radiation Protection
and Measurements (NCRP) as the Program Committee (March 27-28, 2023, Bethesda,
USA).

II. Acceptance of visitors from overseas for briefing and training (10 people)
Acceptance of trainees from overseas through the Nagasaki Association for Hibakushas’
Medical Care (NASHIM) and the like, was completely canceled in FY2022 again; however,
the training of the International Council for Health Care of Radiation-exposed (HICARE) was
resumed to provide online lectures.

15

（Attachment 2）

FY2022
Joint programs between RERF and overseas researchers/research organizations
In italics: Funding Organization
1. Collaborative studies between RERF and US National Cancer Institute (NCI)(1) Under the research contract entered into by and between RERF and the US National
Cancer Institute (NCI), in which Kotaro Ozasa, Former Department Chief of
Epidemiology, served as a responsible person of the RERF side, analysis of solidcancer incidence risks in the LSS cohort, site-specific cancer studies based on
histopathological diagnoses were conducted based on this contract.
The following papers have been published (RERF authors underlined):
Yoshida N, Fujihara M, Preston DL, Ozasa K, Hida A, Ohishi W, Sakata R, Mabuchi
K. Further analysis of incidence of multiple myeloma among atomic bomb survivors,
1950-1994. Blood Advances 2023/02/11 [Epub]:1-10 [RP-3-94]
Utada M, Brenner AV, Preston DL, Yamada M, Grant EJ, Sugiyama H, Sakata R,
Cahoon EK, Ozasa K, Mabuchi K. The effect of prostate-specific antigen (PSA) teston radiation risk estimate for prostate cancer incidence among atomic-bomb survivors.
Radiat Res [in press][RP-S5-19]
Note: The contract research agreement between RERF and NCI, dated May 20, 2019,
expired on July 31, 2021.
(2) Ritsu Sakata, Assistant Department Chief, and Alina Brenner, Senior Scientist,
Department of Epidemiology, are joining with the data of tumor of the central nervous
system from RERF as a part of the pooled analysis conducted by the scientists ofRadiation Epidemiology Branch, NCI.
(3) Ritsu Sakata, Assistant Department Chief of Epidemiology, is joining with the data ofradiation-associated thyroid cancers from RERF as a part of the pooled analysis
conducted by the scientists of Radiation Epidemiology Branch, NCI.
2.

Collaboration between RERF and the/Asia Cohort Consortium (ACC)
Ritsu Sakata, Assistant Department Chief of Epidemiology, is joining the collaborative
project with the ACC entitled: Tobacco smoking, alcohol drinking, body mass index andrisk of rare cancers.

3.

Collaboration between RERF and Institute of Cancer Research, UK and US National Instituteof Environmental
Alina Brenner, Senior Scientist, Department of Epidemiology, is joining withpremenopausal breast cancer data from RERF as a part of the pooled analysis conducted by
Dr. Anthony Swerdlow of Institute of Cancer Research, UK, and Dr. Hazel Nichols of US
National Institute of Environmental.

4.

Collaboration between RERF and University of Washington
RERF entered into a research contract with the University of Washington (Department of
Epidemiology and Department of Biostatistics), for which Richard Sposto, Department
Chief of Statistics served as coordinator. Under this contract, RERF supported the training
and education of MS and PhD students in epidemiology and biostatistics and conductedcollaborative research with students and their advisors. Research projects focused on
analyses of cancer incidence and mortality outcomes in the LSS, as well as the developmentof new statistical methods for analyzing LSS cohort data.

16

Note: The contract research agreement between RERF and the University of Washington,
dated September 16, 2017, expired on December 31, 2021.
5.

RERF international collaborative studies on statistical analyses
Munechika Misumi, Assistant Department Chief of Statistics, continued a collaboration
study with the investigators at Helmholtz München on the mechanistic modeling ofcarcinogenesis having online meeting.

6.

RERF international collaborative studies on radiation dosimetry.
Harry Cullings, Consultant, and Sachiyo Funamoto, Section Chief, Department of Statistics,
collaborated with an international group of dosimetry experts in work to update RERF
radiation dosimetry.

7.

University of Bern international multi-institutional collaborative studies on thyroid
Misa Imaizumi, Assistant Department Chief of Clinical Studies (Nagasaki), Waka Ohishi,
Department Chief of Clinical studies and Michiko Yamada, Division Chief of Radiology of
Department of Clinical Studies are joining with Adult Health Study data from RERF as apart of the pooled analysis of thyroid conducted by Dr. Rodondi of University of Bern,
Switzerland (Thyroid Studies Collaboration).

17令和4年度 外部資金研究一覧表
FY2022 External Research Funds

厚生労働省
Ministry of Health, Labour and Welfare (MHLW)

2

研究資金（資金拠出機関からの入金額）
Research funds(amount of funds from funding¥1,450,000

独立行政法人 日本学術振興会（文部科学省所管の独立行政法人）
Japan Society for the Promotion of Science (JSPS)

7¥11,050,000

一般財団法人 土谷記念医学振興基金
Tsuchiya Memorial Medical Foundation

1¥1,000,000

国立研究開発法人 国立がん研究センター
National Cancer Center

1

総合計

11

外部機関名称
Name of Outside Organization

件数
Number of
Grants18[Independent administrative entity under the jurisdiction of the Ministry of Education, Culture,
Sports, Science and Technology (MEXT)]Grand total

注）・ 間接費を含む。
・ 研究分担者の配分額を含む。
* 研究協力者として研究参画のため、配分資金の配分なし。
Notes)
・ These amounts include indirect cost.
・ These amounts include subsidies allocated to collaborators.
* No research funds are allocated, because the RERF researcher takes part in the research as a cooperative investigator.

¥0 *¥13,500,000令和4年度 外部資金研究一覧表
FY2022 External Research Funds

研究のタイトル
Title of Research

委託組織の名前と場所及び研究グループのチーフ又は担当の主任研究者
Name and location of entrusting outside organization
Chief of research group or principal investigator in charge

放影研における研究者の名前
Investigator(s) at RERF

研究資金（資金拠出機関からの入金額）
Research funds(amount of funds
from fundingorganizations)

令和4年度
令和4年度
開始日
終了日
関連RP
First project
Last project
Related RPs
date in FY2022 date in FY2022

関連性
Relationship to
RERF's mission

疫学部
Department of Epidemiology
1 社会経済的格差に着目したがん対策に資する空間
疫学的ビッグデータ解析研究
Spatial epidemiological big data analysis research that
contributes to cancer control focusing on socioeconomic disparities

192

国際比較可能ながん登録データの精度管理および他の統計を併用したがん対策への効果的活用の研究Studies on the quality control of internationallycomparable cancer registry data and on the effective
usage for cancer control using other statistics

3

科学的根拠に基づくがんリスク評価及び予防ガイド
ライン提言に関する研究
Study for evaluation of cancer risk amd proposal ofcancer prevention guidelines on the basis of scientificevidence

日本学術振興会・科学研究費助成事業「基盤研究（B) 」
研究代表者 伊藤 秀美
JSPS Grant-in-Aid for Scientific Research
Scientific Research (B)Hidemi Ito

研究分担者(Collaborator)
杉山 裕美
Hiromi Sugiyama

March 31, 2023

RP-S2-17

日本人のがんの疫学研究
Epidemiological study of cancer
in Japanese population¥600,000

April 1, 2022

March 31, 2023

RP-S2-17

日本人のがんの疫学研究
Epidemiological study of cancer
in Japanese population

研究協力者のため、研究資金の配分なし
Since this person is acooperative
investigator, researchfunds were notallocated to her.

April 1, 2022

March 31, 2023

RP-A2-15

日本人のがんの疫学研究
Epidemiological study of cancer
in Japanese population

間接経費(Indirect cost)¥60,000

厚生労働省・厚生労働科学研究費補助金
研究分担者「がん対策推進総合研究事業」(Collaborator)
研究代表者 松田 智大
杉山 裕美
国立研究開発法人国立がん研究センター
Hiromi Sugiyama
がん対策研究所 国際政策研究部 部長
Health and Labour Sciences Research Grants (MHLW)
Promotion of Comprehensive Research Project for Cancer
Control
Tomohiro Matsuda
Chief, Division of International Health Policy Research,
National Cancer Center, Institute for Cancer Control

国立がん研究センター・国立がん研究センター研究
開発費
研究代表者 井上 真奈美
国立研究開発法人国立がん研究センター
がん対策研究所 予防研究部 部長
National Cancer Center
Funds for Cancer Research and Related Technology
Development
Manami Inoue
Chief, Division of Prevention,
National Cancer Center, Institute for Cancer Control

April 1, 2022

直接経費
(Direct cost)¥200,000

研究協力者(Cooperative Investigator)
歌田 真依
Mai Utada令和4年度 外部資金研究一覧表
FY2022 External Research Funds

研究のタイトル
Title of Research

委託組織の名前と場所及び研究グループのチーフ又は担当の主任研究者
Name and location of entrusting outside organization
Chief of research group or principal investigator in charge

放影研における研究者の名前
Investigator(s) at RERF

研究資金（資金拠出機関からの入金額）
Research funds(amount of funds
from fundingorganizations)

令和4年度
開始日
First projectdate in FY2022¥850,000

April 1, 2022

March 31, 2023

RP 2-75
RP 6-08
RP 1-15

広範囲な医学的調査（生活習慣病）
Broad-based
medical research(Lifestyle disease)

直接経費(Direct cost)¥0

April 1, 2022

March 31, 2023

RP 6-70
RP 5-90
RP-S2-15
RP 5-02
RP-P2-19

がん研究（被爆者がん研究への応用）
Cancer research(Application to cancer researchamong A-bomb survivors)

RP 6-70
RP 5-90
RP-S2-15
RP 5-02

がん研究（被爆者がん研究への応用）
Cancer research(Application to cancer researchamong A-bomb survivors)

令和4年度
終了日
関連RP
Last project
Related RPs
date in FY2022

関連性
Relationship to
RERF's mission

臨床研究部
Department of Clinical Studies
1

2

生涯にわたる循環器疾患の個人リスクおよび集団リスクの評価ツールの開発及び臨床応用のための研究
Assessments and clinical application of long-term
predictability of cardiovascular risk factors in bothindividual and population levels

20

被爆による造血器腫瘍発症に関与する分子機構の解明と今後への展望
Identification of molecular mechanisms related todevelopment of hematological malignancies byatomic-bomb

厚生労働省・厚生労働科学研究費補助金「循環器疾患・糖尿病等生活習慣病対策総合研究事業」

研究代表者 村上 義孝
東邦大学医学部 教授
Health and Labour Sciences Research Grants (MHLW)
Comprehensive Research on Life-Style Related Diseases
including Cardiovascular Diseases and Diabetes Mellitus
Yoshitaka Murakami
Professor,
Graduate School of Medicine, Toho University

日本学術振興会・科学研究費助成事業「若手研究 」
研究代表者 吉田 稚明
JSPS Grant-in-Aid for Scientific Research
Early-Career Scientists
Noriaki Yoshida

研究分担者 (Collaborator)
立川 佳美
Yoshimi Tatsukawa
研究協力者(Cooperative Investigator)
山田 美智子Michiko Yamada
栗栖 智
Satoshi Kurisu

研究代表者 (P.I.)
吉田 稚明
Noriaki Yoshida

間接経費(Indirect cost)¥0
補助事業期間延長により、令和3年度の未執行額（399,928円） を使用。令和4年度に新たな助成金の交付はなし。
With extension of the funded term, the unexecutedamount for FY2021 (399,928yen) was used. No grant wasprovided for FY2022.

3

被爆後早期に発症した白血病症例の分子病理学
的解析
Pathological and molecular characterization ofleukemia developed shortly after A-bomb radiation
exposure

一般財団法人 土谷記念医学振興基金研究代表者 吉田 稚明
Tsuchiya Memorial Medical Foundation
Noriaki Yoshida

研究代表者 (P.I.)
吉田 稚明
Noriaki Yoshida¥1,000,000

April 1, 2022

March 31, 2023

令和4年度 外部資金研究一覧表
FY2022 External Research Funds

研究のタイトル
Title of Research

委託組織の名前と場所及び研究グループのチーフ又は担当の主任研究者
Name and location of entrusting outside organization
Chief of research group or principal investigator in charge

放影研における研究者の名前
Investigator(s) at RERF

研究資金（資金拠出機関からの入金額）
Research funds(amount of funds
from fundingorganizations)

令和4年度
開始日
First projectdate in FY2022

令和4年度
終了日
関連RP
Last project
Related RPs
date in FY2022

関連性
Relationship to
RERF's mission

統計部
Department of Statistics
1 Fused-lassoによる広島・長崎の被爆に関する時空間リスク推定モデルの開発
Development of a spatio-temporal risk estimation modelfor Hiroshima and Nagasaki exposures by Fused-lasso

日本学術振興会・科学研究費助成事業「基盤研究（B) 」
研究代表者 山村 麻理子
JSPS Grant-in-Aid for Scientific Research
Scientific Research (B)Mariko Yamamura

研究代表者 (P.I.)
山村 麻理子Mariko Yamamura

直接経費(Direct cost)¥3,700,000

研究分担者 (Collaborator)
坂田 律
Ritsu Sakata

間接経費(Indirect cost)¥1,110,000

April 1, 2022

March 31, 2023

RP 1-75

LSS
LSS

RP-S4-18
RP18-61

LSS
LSS

広島大学の研究分担者への配分額は、上記の研究資金に含まれている。
The above amount includes funds allocated to thecollaborators at Hiroshima University.

2 疫学データに基づく大腸がんの放射線発がん機序

21

モデリングとその妥当性の検討
Biology-based mechanistic modelling of colorectal
cancer based on epidemiological data and investigationsof its validity

日本学術振興会・科学研究費助成事業「基盤研究（C) 」
研究代表者 三角 宗近
JSPS Grant-in-Aid for Scientific Research
Scientific Research (C)Munechika Misumi

研究代表者 (P.I.)
三角 宗近
Munechika Misumi

直接経費(Direct cost)¥1,800,000
間接経費(Indirect cost)¥540,000

April 1, 2022

March 31, 2023

令和4年度 外部資金研究一覧表
FY2022 External Research Funds

研究のタイトル
Title of Research

委託組織の名前と場所及び研究グループのチーフ又は担当の主任研究者
Name and location of entrusting outside organization
Chief of research group or principal investigator in charge

放影研における研究者の名前
Investigator(s) at RERF

研究資金（資金拠出機関からの入金額）
Research funds(amount of funds
from fundingorganizations)

令和4年度
開始日
First projectdate in FY2022

令和4年度
終了日
関連RP
Last project
Related RPs
date in FY2022

関連性
Relationship to
RERF's mission

分子生物科学部
Department of Molecular Biosciences
1 放射線の遺伝影響研究を目的として、マウス精原細胞の染色体に構造変異を持ち込む
Introduction of chromosome structural changes into
mouse spermatogonia cells for the analysis of theirtransmission to next generation

2 ヒト造血幹細胞における放射線誘発変異の全ゲノムシーケンスによる解析
Whole-genome sequence analysis of radiation-induced
somatic mutations in human hematopoietic stem cells

22

日本学術振興会・科学研究費助成事業｢基盤研究 (C)｣研究代表者 野田 朝男
JSPS Grant-in-Aid for Scientific Research
Scientific Research (C)Asao Noda

研究代表者 (P.I.)
野田 朝男
Asao Noda

直接経費(Direct cost)¥1,000,000

研究分担者 (Collaborator)
濱﨑 幹也
Kanya Hamasaki

間接経費(Indirect cost)¥300,000

日本学術振興会・科学研究費助成事業「基盤研究（C） 」
研究代表者 田邉 修
JSPS Grant-in-Aid for Scientific Research
Scientific Research (C)Osamu Tanabe

研究代表者 (P.I.)
田邉 修
Osamu Tanabe

直接経費(Direct cost)¥1,600,000

研究分担者 (Collaborator)
松田 由喜子(分子生物科学部）
Yukiko Matsuda(Dept. Molecular Biosciences)
吉田 健吾（分子生物科学部）
Kengo Yoshida（Dept. Molecular Biosciences）
内村 有邦（分子生物科学部）
Arikuni Uchimura（Dept. Molecular Biosciences）

間接経費(Indirect cost)¥480,000

April 1, 2022

March 31, 2023

RP-P3-17

GS細胞染色体への構造変異導入
Introduction of chromosome
structural changes by gene editing
technology

April 1, 2022

March 31, 2023

No RP

放射線被曝による晩発障害である白血病、固形腫瘍、循環器疾患などの分子メカニズムの解明と、それら疾患の予防法、治療法の開発に貢献
This study contributes to theelucidation of molecularmechanisms of the late-onset
diseases by radiation exposure,including leukemia, solid tumors,and cardiovascular diseases, andcontributes to the development ofpreventive and therapeuticmeasures for those diseases.

令和4年度 外部資金研究一覧表
FY2022 External Research Funds

研究のタイトル
Title of Research

委託組織の名前と場所及び研究グループのチーフ又は担当の主任研究者
Name and location of entrusting outside organization
Chief of research group or principal investigator in charge

放影研における研究者の名前
Investigator(s) at RERF

研究資金（資金拠出機関からの入金額）
Research funds(amount of funds
from fundingorganizations)

令和4年度
令和4年度
開始日
終了日
関連RP
First project
Last project
Related RPs
date in FY2022 date in FY2022

関連性
Relationship to
RERF's mission

情報技術部
Department of Information Technology
1 ワイヤレスセンシングと機械学習による猟師向けリアル

タイム獣流推定に関する研究
Study concerning the use of wireless sensing andmachine learning by hunters to estimate the movementsof wildlife real-time

日本学術振興会・科学研究費助成事業「若手研究 」
研究代表者 小野 悟
JSPS Grant-in-Aid for Scientific Research
Early-Career Scientists
Satoru Ono

研究代表者 (P.I.)
小野 悟
Satoru Ono

直接経費(Direct cost)¥200,000
間接経費(Indirect cost)¥60,000

April 1, 2022

March 31, 2023

No RP

診療録を始めとする紙媒体のス
キャンデータを分類するための手法の構築には、本研究で用いる機械学習を用いた行動情報の分類に関する研究が有用に機能すると考えられる。
This research which will
examine machine-learning-based
dog's movement dataclassification, will expect tocontribute to the creation of abest-fit classification method for
medical charts and other paper
documents.

23令和4年度 特別会計一覧表
FY2022 Special Funds
件数
Number of
Funds

資金合計
Amount of Funding
Total

厚生労働省
Ministry of Health, Labour and Welfare (MHLW)

2¥10,701,000

広島県
Hiroshima Prefecture

1¥15,940,947

長崎県
Nagasaki Prefecture

1¥8,700,000

総合計

4¥35,341,947

資金拠出機関名称
Name of Funding Agency

24

Grand total

注）・ 間接費を含む。
・ 研究分担者の配分額を含む。
Notes)
・ These amounts include indirect cost.
・ These amounts may include subsidies allocated to collaborators.

令和4年度 特別会計一覧表
FY2022 Special Funds
研究のタイトル
Title of Research
放射線業務従事者の健康影響に関する疫学
研究
Epidemiological study of health effects inradiation workers

厚生労働省・労災疾病臨床研究事業費補助金
研究代表者 大久保 利晃
独立行政法人労働者健康安全機構 労働安
全衛生総合研究所 労働者放射線障害防止
研究センター センター長

放影研における契約者/
研究者の名前Investigator(s) at RERF

資金拠出機関からの入金額
Amount of Funds
from Funding
Agencies

開始日
Initiation
Date

終了日
Termination
Date

関連RP
Related RPs

関連性
Relationship to
RERF's mission

研究分担者(Collaborative Investigators)
大石 和佳
Waka Ohishi¥8,827,000

April 1,
2022

March 31,2023

厚生労働省・委託事業
丹羽 太貫
MHLW Entrustment
Ohtsura Niwa

受託者(Contractor)
丹羽 太貫
Ohtsura Niwa

¥1,874,000

December 19,
2022

March 31,2023

がん登録推進事業
Cancer Registry Promotional Project

広島県・委託事業
丹羽 太貫Hiroshima Prefecture
Ohtsura Niwa

受託者(Contractor)
丹羽 太貫
Ohtsura Niwa

¥15,940,947

April 1,
2022

March 31,2023

RP18-61
RP29-60
RPs18-61&
29-60附属書

がんの疫学研究、
LSS、胎内被爆者、
F1集団
Epidemiological study of cancer,
LSS, in utero, andF1 populations

長崎県がん登録・評価事業
Nagasaki Prefecture Cancer Registry Program

長崎県・委託事業
丹羽 太貫Nagasaki Prefecture
Ohtsura Niwa

受託者(Contractor)
丹羽 太貫
Ohtsura Niwa

¥8,700,000

April 1,
2022

March 31,2023

RP18-61
RP29-60
RPs18-61&
29-60附属書

がんの疫学研究、
LSS、胎内被爆者、
F1集団
Epidemiological study of cancer,
LSS, in utero, andF1 populations

RP 6-15

Research Grant for Clinical Studies of Work-RelatedIllness (MHLW)
Toshiteru Okubo
Director, Research Center for Prevention from
Radiation Hazards of Workers, National Institute ofOccupational Safety and Health, Japan Organizationof Occupational Health and Safety

1

25

原爆被爆者の生物試料の保管及び活用に関する研究事業2 Research Program on preservation and use of the
A-bomb survivors' biosamples

3

4

委託組織の名前と場所及び研究グループのチーフ又は担当の主任研究者
Name and location of entrusting outsideorganization/Chief of research group or principal
investigator in charge

東電福島第一原発事故処理緊急作業従事者の長期疫学調査
Long term follow-up
epidemiological study on
emergency workers of TEPCO,
Fukushima 1F Nuclear Power
Plant accident.

原爆被爆者の生物試料の保管
及び活用
Preservation and use of the Abomb survivors' biosamples

II. Operation and management of RERF
1. Research Resource Center
In order to accomplish the Strategic Plan of RERF, it is planned that the Research Resource
Center (RRC) will be established with the aims to modernize the research infrastructure of
RERF and to facilitate collaborative studies by streamlining research management system.
More specifically, the mission of the RRC is 3-fold as follows:(1) Preserve RERF's research assets and historical materials, which include various
paper materials for research, photographs, films, paper manuscripts, and datasets.
(2) Integrate all research data and biosample inventories to enhance the availability of
those research resources, and for this aim, provide tools and systems for datavisualization and data assembly.
(3) Create an Office of Research Support to provide an efficient administrative
framework to advance collaborative projects inside and outside RERF and facilitate
applications for contracts and grants.
As the first of the two-step process to initiate the RRC under the recommendation of the
Preparatory Committee for the Establishment of the RRC, the RRC Operating Committee
was established in FY2021. With the retirement of Dr. Grant, Assistant Chief of Research,
who was the chair from the time of the committee’s establishment, Dr. Ono, Chief ofInformation Technology Department (ITD), assumed the chair’s position in January 2023.
In FY2022, the Research Resource Section, as the predecessor of the RRC, was newly
established in ITD. As the endeavor to preserve RERF's research assets and historicalmaterials according to the mission (1) above, microfilms kept by the Departments of
Epidemiology and Clinical Studies were digitized over the two years from 2020. The
physically degraded old microfilms needed to be dealt with urgently. Moreover, in FY2022,
the Section undertook the digitization of photographs, videos, and films kept by the Libraryand Archives Section and the organization and digitization of inventories of pathologicalsamples (such as paraffin blocks and slides) kept by the Department of Epidemiology, andinitiated the digitization of negative films of chromosome images and their ledgers, which
are kept by the Department of Molecular Biosciences. Furthermore, the preparation is being
made to introduce a Content Management System for the centralized management of paperbased materials including paper manuscripts and research protocols. Further, according to
the mission (2) above, the preparation is also being made to introduce a Data Management
System to enhance the availability of RERF's research assets, and a pilot project involving
the foundation’s actual data has started. On the other hand, for the mission (3) above, theOffice of Research Support aims to facilitate research activities through the support for
research administrative procedures, the management and use of intellectual property, andthe support for external grant application. To achieve this objective, the preparation is being
made to introduce electronic workflow system for digitization of the foundation’s decisionmaking processes.
2. Review on the relocation of the Hiroshima Laboratory
The candidate site for the Hiroshima Laboratory’s relocation was narrowed down to theHiroshima University’s Kasumi Campus at the 12th Board of Councilors meeting in June
2022 (by mail ballot), and then the laboratory’s relocation was finalized at the 31st
extraordinary Board of Directors meeting in January 2023, and finally RERF submitted an
application to Hiroshima University for acceptance of the relocation. RERF received awritten approval of acceptance of the relocation from the university and carried forward the26plan to relocate the laboratory to the Hiroshima University’s Kasumi Campus. In December
2022, the Cabinet approved the government budget for FY2023, which included part of theconstruction costs of the laboratory’s new building at the relocation site, and the budget
was passed in the Diet session on March 28, 2023.
3. Transition to a full audit
RERF has endeavored to undergo a voluntary audit (full audit) through an external
auditing firm to supplement the audit conducted by its Auditors. In FY2022, the “FY2022
Beginning Balance Investigation” was conducted by Deloitte Touche Tohmatsu LLC.
Tohmatsu’s “Investigation Report,” which was submitted in June 2022, concluded thatTohmatsu could undertake the voluntary audit. Accordingly, an audit contract was signedwith Tohmatsu on September 1, 2022, and a voluntary audit for FY2022 was initiated. The
voluntary audit has been conducted from the date of the contract and will continue throughJune 30, 2023.
The specifics of the voluntary audit, as of the end of March 2023, are as follows:First-round remote audit, December 12–14, 2022
1. Assessment of preparation and implementation of internal control: Process forpurchase, Process for fixed assets management, Inventory, Process for personnel
affairs and salaries, Process for finance, Process for sales, and Business flow.
2. Discussions with the Chairman: Gaining an understanding of the overall businessenvironment and of the Directors’ management processes.
 Second-round audit, March 30, 2023
Substantive procedures taken during the fiscal year: Substantive analyticalprocedures (procedures to determine any material difference between the
expectation values and the book values) Third-round audit, March 31, 2023
Substantive procedures taken during the fiscal year: witnessing for stocktaking,physical inspection of cash, confirmation of bank balances, confirmation with alawyerUpon completion of the voluntary audit, the final report will be submitted to the Auditors
by the regular meeting of the Board of Directors in June 2023.
4. Revision of the rules and regulations
RERF in FY2022 continued to review its regulations to enhance the public interest
incorporated foundation’s operational framework. The following are main regulations
revised or established. As instructed by its auditing firm, the foundation also reviewed its
system to clarify the associations and hierarchical relations among the regulations.
 Regulations Concerning Responses to Antisocial Forces [Effected on April 1, 2022]
Policy of RERF to prevent the damage by antisocial forces was developed, and at the sametime, the regulations were established to block all associations with the antisocial forces
including any transactions with them and to also include response at the time of occurrenceof problems.
 Supplementary Regulations Concerning Organization of the Laboratory (Research
Departments) [Effected on April 1, 2022]
Changes to the names of two of the Dept. of Molecular Biosciences’ laboratories (Cellular27

Genomics and Molecular Pathology) and changes accompanying the abolition of theNEWS Office in the Dept. of Clinical Studies were reflected into the regulations.
 Operational Administrative Regulations for the Core Administrative System under theManagement of the Secretariat [Effected on April 1, 2022]
The rules for the core administrative system under the Secretariat’s management were
established.
 Regulations Concerning Internal Audit [Effected on April 1, 2022]
Overall review of the Regulations Concerning Performance of Internal Audit and theDetailed Regulations Concerning Performance of Internal Audit of External ResearchFunds was conducted to integrate the two regulations into the Regulations Concerning
Internal Audit.
 Regulations on Handling of External Research Funds [Effected on April 1, 2022]
The Regulations on Handling of External Research Funds were established by merging of
the administrative regulations on external research funds.
 Regulations of Safety and Health Committee [Effected on May 1, 2022]
The Safety and Health Committees in Hiroshima and Nagasaki reviewed the requirements
for establishing a committee meeting, and based on the committees’ decision, theRegulations of Safety and Health Committee were established.
 Regulations for Electronic Signature Management [Sept. 28, 2022 (applicability date:
Sept. 1, 2022)]
The regulations pertaining to electronic signature including the administrator, authority
holder, and handling of electronic signature were established to correspond to the use ofelectronic contracts requested from outside.
 Standards for Handling of Outside Congratulations/Condolences [November 1, 2022]
The standards were newly established by reviewing how the outside congratulations/condolences were being handled.
 Travel Reimbursement Regulations [December 1, 2022]
The Travel Reimbursement Regulations were revised following review of the regulations
by the section in charge to facilitate the paperwork for the disbursement of official travel
expenses and fair cost disbursement.
 Guidelines for Establishment of External Advisory Committee on Biosample Usage[Effective date: March 1, 2023]
With establishment of the “External Advisory Committee on Biosample Usage,” theseguidelines for the operation of the committee were established.
5. Facility upgrades
Nagasaki Laboratory replaced A/C units with FY2022 subsidy for major facility renovations
including health and sanitation facilities from the Ministry of Health, Labour and Welfare.

28

Appended documents to FY2022 report of activities

There were no items considered to be important matters for supplementing thecontents of the FY2022 report of activities.