Table of Contents
From the Editors ......................................................................................................................................... 1
Special Message from RERF Chairman ..................................................................................................... 1
RERF NewsThe 38th Scientific Council Meeting .................................................................................................... 2
Visit by Hiroshima Governor Hidehiko Yuzaki ..................................................................................... 5
Activities Reports in Fukushima and Yamagata Prefectures ................................................................. 6
Transition to Exceptional Incorporated Foundation with Councilors ................................................... 8
Visit by Officials of Fukushima Medical University ............................................................................. 9
Staff News ............................................................................................................................................. 9Awards Received by RERF Scientists ................................................................................................. 11
Conference and Workshop Reports
Mini-workshop: Roles of Smoking on Radiation Risk of Lung Cancer, by Nori Nakamura ............. 12
Workshop on Potential Extensions to DS02 Organ Dose Calculations, by Harry M. Cullings .......... 14
Science Articles
Highlights of RERF Departments: Research Activities of the Department of Epidemiology,
by Kotaro Ozasa and Akihiko Suyama ............................................................................................ 15
Highlights of RERF Departments: Research Activities of the Department of Statistics,
by Harry M. Cullings ...................................................................................................................... 22
Human Interest Notes
In the Beginning, by William J. Schull................................................................................................ 28
Reaching Retirement Age, by Kazuo Neriishi .................................................................................... 30
Research Protocols and Publications
Research Protocols Approved in November 2010–April 2011 ........................................................... 32
Recent Publications ............................................................................................................................. 33

This newsletter is published by the Radiation Effects Research Foundation (formerly the Atomic
Bomb Casualty Commission), established in April 1975 as a private, nonprofit Japanese foundation.
It is supported by the government of Japan through its Ministry of Health, Labour and Welfare andthat of the United States through the National Academy of Sciences under contract with the
Department of Energy.
RERF conducts research and studies—for peaceful purposes—on the medical effects of radiation on humans with a view toward contributing to the maintenance of the health and welfare of
atomic-bomb survivors and to the enhancement of the health of all mankind.
Editor-in-Chief: Evan B. Douple, Associate Chief of ResearchTechnical Editor: Yuko Ikawa, Public Relations & Publications Office
Editorial Policy
Contributions to Update receive editorial review only and do not receive scientific peer review.
The opinions expressed herein are those of the authors only and do not reflect RERF policies orpositions.
Contact: Mailing address: RERF Public Relations & Publications Office, 5-2 Hijiyama Park,
Minami-ku, Hiroshima 732-0815 Japan
Telephone: 81-82-261-3131; Facsimile: 81-82-263-7279
Internet: www.rerf.jp

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From the Editors, Special Message from RERF Chairman

From the Editors
Welcome back!
The year 2011 was looking a lot like any otheryear, perhaps with a little longer and colder thannormal winter. The rice was pounded into mochi by
RERF employees at the New Year Party, and theannual meeting of the Scientific Council was concluded after much preparation by RERF’s researchstaff. But on March 11, one of the world’s largest
earthquakes generated an unusually large tsunami
and RERF’s typical scheduled activities were about
to change. One of us [EBD] will never forget walking down the stairs into the clinical studies reception area and seeing RERF’s chairman watching
the breaking news live on a large television screen;
Dr. Okubo turned to me and said “There has been alarge tsunami in Tohoku, the northern-most part ofJapan’s island of Honshu—and it is not good.” In
the days that followed, the news turned to focus on
the effects of the Fukushima Dai-ichi nuclear
power plants. The world turned its attention to thecountry that had previously suffered exposure toradiation and to the institution whose studies of the
A-bomb survivors have contributed major information for mankind’s risk estimates about radiation
health effects. Ironically, on March 14, the American Medical Association’s Journal of Disaster
Medicine and Public Health Preparedness would
publish a special supplement titled “Nuclear Pre-

paredness” that would include a cover-story article
reviewing the work and findings of the ABCC
and RERF. In this issue of Update, please read
Chairman Okubo’s message about RERF’s role inthe continuing disaster and personal accounts of
RERF employees who were sent to assist the survivors in Tohoku.
In addition to other news regarding RERF, youwill also find in this issue a report on the 38th
Scientific Council meeting, an update on RERF’s
transition to a public-interest incorporated foundation, reports of two workshops held at RERF, andtwo articles describing the research activities of thedepartments of Epidemiology and Statistics.
Finally, two human interest notes are included by
two long-term supporters of ABCC and RERF,
William “Jack” Schull and Kazuo Neriishi.
The cherry blossoms (sakura) and other signs ofspring would eventually emerge, but Ohanami
Parties were much less frequent and more subdued
as thoughts continually turned to those mostafflicted in the north as efforts continue to attempt
to resolve the power plant conditions. Meanwhile,
thanks to RERF’s Midori no Kai (Green ThumbClub), employees were cheered up daily by a beautiful planting that spelled out “RERF.” We hopethat you will enjoy this issue and don’t hesitate tolet us know how we might improve our reporting of
RERF’s many activities.
Mata oidekudasai (goodbye and please comeagain),

Evan B. Douple
Editor-in-Chief

Cherry blossoms in full bloom and “RERF” letters in phlox
flowers

Yuko Ikawa
Technical Editor

Special Message from Chairman Toshiteru Okubo
We would like to offer our deepest condolences
to all those affected by the recent earthquake thatstruck in Japan’s Tohoku region. In response to theaccident at the Fukushima Dai-ichi nuclear power
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plant, RERF has enhanced our activities with otherrelated organizations for support of medical countermeasure efforts, including the dispatch of radiation specialists to the affected region. (See articles
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RERF Newson the activities reports in Fukushima and Yamagata
on pages 6–8.)
It is hoped that the radiation-related information
posted on our website can help resolve any questions and concerns about radiation. We also fervently hope and pray for the affected region’stimely recovery.
We have thus far screened 30 individuals coming from Fukushima Prefecture for radioactive
contamination, but no one needed decontamination. Since it is expected that there will be moresuch requests, we will coordinate such efforts with
Hiroshima University and the Hiroshima Red
Cross Hospital & Atomic-bomb Survivors Hospital, as the designated dosimetry organizations in
Hiroshima Prefecture. In addition, we are participating in a Chromosome Network, and will assist
with the dosimetry of workers at the nuclear plantby analyzing chromosome images sent by the
National Institute of Radiological Sciences.
RERF’s website has been expanded to provide
additional radiation-related information to the general public. The traffic to the site has soared since
the nuclear accident, and the number of visitors ona peak day was equivalent to that of four months
normal traffic. Even today, daily traffic to the site
continues to be that of a former two months. We
received numerous telephone inquiries in the week

Members of the Hiroshima Prefectural Police, after theirreturn from providing assistance in Fukushima Prefecture,undergo screening for contamination at RERF (see also
cover photo).

following the accident, particularly from the members of the media, but the number of calls has now
decreased. The Public Relations and Publications
Office is responding to such inquiries utilizing thetechnical expertise of RERF’s research scientists.
RERF is able to contribute to the design andimplementation of long-term epidemiologicalfollow-up research, and is preparing to respond tosuch requests promptly.

Report on the 38th Scientific Council Meeting, 2011
The 38th Scientific Council (SC) met fromFebruary 28 to March 2, 2011 in Hiroshima, Japanto review RERF’s scientific programs. It was cochaired by Dr. Kiyoshi Miyagawa and Dr. David
Hoel. Dr. Kazuo Tajima, Director of the Aichi
Cancer Center Research Institute, joined the SC
with the expiration of the term of Dr. Yoshiharu
Yonekura. Four additional experts were invited to
be special councilors to assist the SC in an in-depth
review of the Departments of Epidemiology andStatistics. They were Dr. Suminori Kono of Kyushu
University, Dr. T. Shun Sato of Kyoto University,
Dr. John Boice of Vanderbilt University, and Dr.
Colin Begg of Memorial Sloan-Kettering Cancer
Center.
RERF Chairman Dr. Toshiteru Okubo welcomed
the SC members and guests and expressed how
important the SC’s work is to the staff of the RERF.
He also briefly explained some changes that will
come about as RERF becomes a public-interest
incorporated foundation. The Scientific Councilors
will become the Scientific Advisors (Scientific
Advisory Committee) who will continue to review
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the scientific programs of RERF.
Responses to last year’s SC general recommendations and highlights of research accomplishments during 2010 were summarized by Dr. Roy
Shore. In response to the 2010 SC recommendations, we have made progress in integrating andfocusing on RERF project priorities. Departments
have held meetings or mini-retreats to define study
priorities and achievement milestones. Experiencehas shown that both broad, thematic working
groups and smaller, more focused “mini-working
groups” are beneficial, so both are being used strategically. Regarding a centralized database that
integrates all available information and biosamples
on study participants, a key issue is having a userfriendly database system that is fully cross-indexedand documented and can be accessed in a variety ofways. RERF committees on data and biosample
management are currently working on various
aspects of this. Regarding increased statistical bioinformatics support, the Statistics Department has
been conducting bioinformatics seminars and is
working with the basic science departments on
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RERF News
studies that have large arrays of genetic or phenotypic measurements. Regarding increased firstauthored publications and mentoring of young scientists, departmental leaders have been asked tomonitor progress on publications and to develop
plans for mentoring.
Accomplishments during 2010 include the initiation of the F1 longitudinal clinical examination
program for nearly 12,000 F1 participants, and thecompletion of the initiative that added 1,900 new
screenees under the age of 10 years at the time of
the A-bomb to the Adult Health Study (AHS) in
order to strengthen the study’s precision in estimating risks after childhood exposure. An international
workshop was held on the epigenetic effects ofradiation, which stimulated internal research on
epigenetic radiation effects. Significant progresshas been made in updating the tumor registries andthe dosimetry databases. Major publications thispast year pertained to radiation risk for heart disease, myelodysplastic syndrome, cataracts, andsecond primary cancers, the development of atooth-enamel-based neutron biodosimeter, and thejoint effects of radiation and smoking on lung cancer risk.
Several important new projects were initiatedduring 2010. To follow-up on the early ABCC findings regarding cognitive deficits among those within utero radiation exposure, a study was initiated onlate-life neurocognitive function among AHS participants exposed in utero or in early childhood. To
learn more about the mechanisms by which radiation exposure may increase the risk of circulatory
diseases, new AHS studies have been implemented
on physiological indices of arteriosclerosis and on
measurements of circulatory disease-related cytokines. To experimentally verify radiation-related
circulatory disease effects at moderate doses, a
study of the incidence of hypertension and stroke isbeing undertaken over the dose range of 0–4 Gy ina strain of rats susceptible to the two endpoints.
A summary review of scientific transparency
and data sharing at RERF was given. Over 10
major RERF datasets are publicly available on our
external website. They have been widely accessed
as researchers from 41 different countries havemade about 470 data downloads in the past three
years. Furthermore, during 2010 more than 60
studies with external collaborators were ongoingthat involved individual data or biospecimen sharing.
The general recommendations this year by the
SC included the following:• Clear articulation of the justification, prioritization, and overall quality of each research
project is needed. Research proposals (RPs)need to address topics of compelling releReturn to Table of Contents

3vance to current scientific knowledge and better articulate the scientific rationale. A clear
written framework for RPs would be helpful,as well as assigning priority scores to RPs.
• Contemporary scientific advances increasingly require inter-disciplinary collaborations
and separate programmatic structures to facilitate them. The program themes should beselected on the basis of the overarchingresearch priorities of RERF, and these could
be periodically updated to reflect the contemporary landscape of research emphasis.
• The many and varied databases of participant
information and biological samples should be
integrated into a central database for the useof researchers in all departments. The database would also require user-friendly database software that researchers could use to
retrieve the data.
• Biological samples are a very important scientific asset of RERF. Since current biosample
storage space will soon be filled, RERF must
give the highest priority to finding space forthese unique biological samples.
• With the limited availability of government
research funds it is important to facilitate
applications for extramural funding. It is also
important that travel funds for international
scientific meetings be protected, so that RERF
scientists can present their seminal findings to
the world as well as stay current on the latest
research relevant to radiation health effects.
• Collaborations with universities and otherJapanese colleagues should be strengthened,
and more graduate students and postdoctoral
fellows should be recruited to engage in
research based on RERF’s unique resourcesand databases.
• High quality publications are essential for
informing the world of new findings and forthe continued success of RERF. More such
publications are needed.
Highlights of some of the main recommendations for individual departments or offices are:• Pilot studies should incorporate clear milestones for making decisions on when the
results of the pilot study indicate a high probability of success for a larger scale study versus when a study should not be pursued further.
• As much as possible, a full range of confounding factors should be considered ininterpreting study results.
• An updating of the denominators for the Life
Span Study (LSS) cancer incidence studies
will be of much value.
• Comparing disease rates in RERF epidemioRERF Update Volume 22, Issue 1, 2011

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RERF News
logic cohorts with general population rates
can be useful. Such population comparisons
add an additional perspective, especiallywhen evaluating rare outcomes such as mesothelioma.
• Collaborative work should enjoy high priority
in the overall mission of the Department of
Statistics. The reviewers are pleased that the
department takes a proactive approach to consulting, beginning with early involvement instudy design.
• Original research on statistical methodology
should continue to be an important goal of theStatistics Department. This will encourage theprofessional staff to maintain an interest in
developments in the field, generally enliven
the intellectual environment, and ideally bringrecognition to the department.
• The F1 offspring are still young and further
follow-up is highly recommended. It should
be noted that this type of study has not been
undertaken anywhere else in the world.
• The F1 clinical examination program should
consider a systematic examination of F1 study
subjects for congenital defects.
• Investigation of the biological significance of
ALK rearrangements newly found in papillary
thyroid cancer is needed to clearly support
their role in carcinogenesis. Establishment of
mammalian cells or transgenic mice harboring the rearranged ALK gene should be a highpriority.
• The pilot influenza vaccination study shouldincorporate a careful evaluation of previous
infections and the previous vaccination history of each subject.
• More comprehensive genomic approaches,such as multiplex single nucleotide polymorphism (SNP) typing for multiple candidate
genes, genome-wide SNP typing, andgenome-wide array-based methylation assays

should be considered and encouraged whereappropriate.
• Even in its transition years, the Genetics
Department should act as the genetic counselor to the entire enterprise, bringing awareness and access to all the astonishing advancesin genetics and genomics as applied to themission of RERF.
• As the first test of the methodology of nextgeneration DNA sequencing, the sequencingof chromosome 19 is planned for some study
subjects. A long-term strategy for future massive sequencing of a large number of family
samples should also be considered.
• The analysis of copy number variants using
high-density microarrays in mouse strains has
provided a sound basis for this technology in
the Genetics Department. The technology is
now ready for extending to the study of thegenetic effects of atomic-bomb radiation.
• Sample collection and storage activities
should be consolidated in a specialized support section, rather than being the responsibility of individual research sections.
• Emphasis should be given to producing wellwritten press releases at the time of major
RERF publications.
In summary, the SC highlighted the unique roleof RERF in informing the world about radiation
effects, and they called for additional attention toresearch priorities, inter-disciplinary and collaborative research, integrated databases, and publication
productivity.
RERF Scientific Councilors
Dr. David G. Hoel, Co-chairperson, Distinguished
University Professor, Department of Medicine,
Medical University of South Carolina
Dr. Kiyoshi Miyagawa, Co-chairperson, Professor,

Participants of the 38th Scientific Council meeting (Hiroshima Laboratory)
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RERF Update Volume 22, Issue 1, 2011

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RERF News
Laboratory of Molecular Radiology, Center for
Disease Biology and Medicine, Graduate
School of Medicine, The University of Tokyo
Dr. Takashi Yanagawa, Professor, The Biostatistics
Center, Kurume University
Dr. Katsushi Tokunaga, Professor, Department of
Human Genetics, Division of International
Health, Graduate School of Medicine, The
University of Tokyo
Dr. Kazuo Sakai, Director, Research Center for
Radiation Protection, National Institute ofRadiological Sciences
Dr. Kazuo Tajima, Director, Aichi Cancer Center
Research InstituteDr. Marianne Berwick, Professor and Chief, Division of Epidemiology and Biostatistics andAssociate Director, Cancer Research and Treatment Center, University of New Mexico
Dr. John J. Mulvihill, Children’s Medical ResearchInstitute/Kimberly V. Talley Chair in Genetics;
Professor of Pediatrics; Head, Section of
Genetics, University of Oklahoma Health
Sciences Center

Dr. Michael N. Cornforth, Professor and Directorof Biology Division, Department of Radiation
Oncology, University of Texas Medical Branch
Dr. Sally A. Amundson, Associate Professor of
Radiation Oncology, College of Physicians andSurgeons of Columbia University
Special Scientific Councilors
Dr. John D. Boice, Jr., Professor of Medicine,
Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center
Dr. Colin Begg, Chairman, Department of Epidemiology and Biostatistics, Eugene W. Kettering
Chair, Memorial Sloan-Kettering Cancer Center
Dr. Suminori Kono, Professor, Department of Preventive Medicine, Kyushu University Facultyof Medical Sciences
Dr. T. Shun Sato, Professor, Department of Biostatistics, Kyoto University School of Public
HealthHiroshima Governor Hidehiko Yuzaki Visits RERF
In the morning of January 19, Hiroshima Governor Hidehiko Yuzaki, who assumed his office inNovember 2009, visited the Hiroshima Laboratory.
He received briefings at the Chairman’s office fromDr. Kazunori Kodama, Chief Scientist, on RERF’s
research and then from Dr. Toshiteru Okubo,
Chairman, on RERF’s current status and futureplans. Afterwards, Governor Yuzaki spoke with thedirectors and senior staff, and toured the RERF
facilities led by Dr. Okubo and Mr. Eiji Akimoto,Chief of Secretariat.
After the Fukushima Dai-ichi nuclear power
plant accident, Governor Yuzaki emphasized theimportance of utilizing the knowledge and experience accumulated in Hiroshima and Nagasaki forover 60 years. He announced that utmost cooperation will be extended to the long-term health management of Fukushima residents in the future,including training for doctors, nurses, and radiological technicians, through the Hiroshima Interna-

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tional Council for Health Care of the Radiationexposed (HICARE), consisting of Hiroshima
Prefecture, Hiroshima City, RERF, and other
A-bomb-related organizations in Hiroshima.

Hiroshima Governor Hidehiko Yuzaki (left) touring RERF
with guidance from Chairman Toshiteru Okubo (far right)

RERF Update Volume 22, Issue 1, 2011

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RERF News

Dispatch of RERF Staff to the Area Affected by the Fukushima
Dai-ichi Nuclear Power Plant Accident
In response to the accident at the Fukushima Dai-ichi nuclear power plant, RERF received two
requests regarding the dispatch of radiation specialists in March 2011. At the request of theHiroshima International Council for Health Care of the Radiation-exposed (HICARE), Mr.
Toshinori Kurisu (radiological technician, Department of Clinical Studies, Hiroshima) was dispatched to Fukushima Prefecture as a member of its radiation measurement team. The other request
came from the Yamagata Prefectural Office via the Ministry of Health, Labour and Welfare(MHLW), and Dr. Norio Takahashi (research scientist, Department of Genetics) and Mr. Katsuhisa
Yamasaki (radiological technician, Department of Clinical Studies, Nagasaki) were dispatched tothe prefecture to engage in radiation measurements and provide health consultation. All three completed their duties successfully and returned safely after one week. We have asked them to write
about their experiences in the affected area.

Report on Dispatch to Fukuyama Prefecture
in Response to Tohoku Earthquake
Toshinori Kurisu, Assistant Chief of Technicians
Department of Clinical Studies, Hiroshima

On March 15, the Fukushima prefectural governor (via the Fukushima Prefectural Disaster Countermeasures Office) made an urgent request toHiroshima’s governor for dispatch of radiological
technicians and nurses, to deal with the situation at
the Fukushima Dai-ichi nuclear power plant damaged by the earthquake that struck off the coast ofeastern Japan on March 11. In response, theHiroshima prefectural government requested theHiroshima International Council for Health Care of
the Radiation-exposed (HICARE) to organize anddispatch a radiation dose-measurement team, and I
was dispatched to Fukushima prefecture fromMarch 16 to 22, 2011, as a sub-leader of the teamof six members.
In collaboration with the Fukushima Central
Prefectural Public Health Center (Sukagawa City),
we visited the shelters in the center’s jurisdiction,and conducted screening tests and decontamination
if any contamination was found. We also issued
screening measurement certificates indicating thetest results. None of the measurement values
reached the level requiring decontamination designated by the Fukushima government. We examineda total of 1,447 persons at 12 shelters in five cities
and towns.
For those showing a higher than backgroundlevel but not high enough to require decontamination, we first explained while showing them theirmeasurement results that their clothes such as coats
and socks contained small amounts of radioactive
substances. Even though most of the affected people evacuated their homes without any extra clothes
and could not take a bath or a shower in the shelters, we explained that, as soon as the inconveReturn to Table of Contents

nience that they were experiencing improved, it
was desirable to take the following measures: 1)
take a bath/shower, 2) change clothes, 3) wash theclothing containing radioactive substances aswould be done normally, 4) wipe with a slightly
damp towel the items that cannot be washed, 5)place such items into plastic bags, shut the bags
tightly and store them in a separate area, if theycannot be washed right away, in order to prevent
vaporization of iodine and scattering of radioactive
dust, and 6) wash shoes with water and wipe any
mud off the soles. Among those measures, we wereable to confirm later that bathing and laundering
were effective because we found that there was aclear difference between the values before and after
such measures were taken.
In conducting effective and efficient screeningof radiation contamination for a large number ofresidents without sufficient equipment and manpower, there is a risk of delayed decontamination
treatment due to long waiting times and of secondary contamination via those already contaminated.
In order to avoid such a situation, it is necessary toRadioactive contamination screening for Fukushima residents at Miharu Junior High School, one of the evacuationsites (Toshinori Kurisu, second from right)

RERF Update Volume 22, Issue 1, 2011

RERF News
identify those potentially contaminated as soon as
possible and to decontaminate them promptly toprevent secondary contamination. One solution is
to use environmental measurement equipment tomeasure only the shoe soles of residents instead of
scrutinizing the entire body from the beginning,
triaging those at a certain radiation level for priority screening. By doing so, health hazards can be
reduced and prevented and the spread of contamination avoided.
I would like to express my heartfelt sympathy to
all those affected by the disaster and offer my deepest condolences to the victims. I truly hope that
restoration of the affected areas is achieved at theearliest possible date.

Dispatched to Help People Evacuatedfrom Fukushima Prefecture to
Yamagata Prefecture
Norio Takahashi, Research Scientist,
Department of Genetics
Katsuhisa Yamasaki, Senior Technician,
Department of Clinical Studies, Nagasaki

We were dispatched to Yamagata Prefecture foreight days from March 17 through 24, 2011, at therequest of the prefectural government through the
Ministry of Health, Labour and Welfare. We weretold that our mission would be to measure radiation
contamination levels of people from Fukushima
Prefecture who had been forced by the nuclear
power plant emergency to take refuge in Yamagata
Prefecture. Many people were evacuated from thegovernment-designated evacuation zone. About
1,000 took shelter in the city of Yonezawa. Before
we left Hiroshima, we had seen film footage ofsome officials busily measuring contaminationlevels in the evacuees.
A blizzard warning had been issued in theweather forecast for the city of Yamagata for March
17. We were thus skeptical as to whether or not we
could arrive at our destination. Regardless, we left
for Yamagata. When departing RERF, we received
words of encouragement and advice from Chairman Toshiteru Okubo and many others, with an
emergency food supply and plastic bottles ofwater—a package hastily arranged by the General
Affairs Section and enough for us to survive aweek—in hand. That was the beginning of our“eight extraordinary days.”
Our plane managed to land at Yamagata Airport,
which was buried in more snow than I have everseen in Hiroshima, after dodging many potential
problems on the way. There, we were greeted by
Mr. Hiroyuki Satoh of the Department of Healthand Welfare, Yamagata prefectural government, our
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7host. When we arrived at the Yamagata prefectural
government office, we were surprised to hear thatthe governor was expecting us. During our talkwith the governor and the chief of the Health andWelfare Department, among others, we came tounderstand that our mission was not limited tomeasurement of contamination levels but was actually four-fold: 1) to give advice to those concernedin the local community on establishment of systems for detecting levels of radioactive surface
contamination and removing such radioactive particles; 2) to give lectures on radiation to the staffs
of the prefectural government and local publichealth centers; 3) to inform people who took shelter in Yamagata Prefecture of the radiation doses
people might be exposed to in the prefecture andother relevant information in order to relieve undue
anxiety; and 4) to provide a feeling of security to
the residents of the prefecture through the mass
media. We began our activities in line with the mission.
The evacuees, excluding those who voluntarily
took shelter at private facilities (e.g., hotels), werestaying in groups at about 50 public facilities (e.g.,
gymnasiums). Some facilities, such as the
Yamagata municipal gymnasium, accommodated
more than 1,000 evacuees, while others housed justa handful. All the evacuees were taken care of by
public health nurses affiliated with four local healthcenters, each of which is located in one of the four
administrative districts that the prefecture of
Yamagata is divided into for governance. There isone branch health center in the city of Yamagata.
Therefore, as a first step, we formulated instruction manuals for 1) establishment of definitions ofcontamination and non-contamination, 2) identification of individuals requiring surface contamination tests, 3) surface contamination tests and use of
testing equipment, and 4) removal of radioactive
particles from clothing and the like as well as frombody surfaces, and management and storage ofcontaminated clothes and items used for such
removal. The work was carried out in consultation
with the chiefs of the health centers and representatives of various hospitals in the cities of Yamagata
and Yonezawa, which had received large numbersof evacuees.
As a second step, we gave a lecture to the prefectural government staff, and also visited thehealth centers to brief public health nurses on theabove instructions and radiation. Each of the lectures was attended by 30 to 50 individuals, wholistened with intense interest. Questions those individuals had been asked by evacuees were sharedand possible responses were discussed as casestudies.
We went on to visit six facilities housing evacuees to explain to them that the free-in-air (FIA)RERF Update Volume 22, Issue 1, 2011

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RERF News
radiation doses in Yamagata Prefecture posed no
danger to human health. Some evacuees said thatthe information regarding the area of their original
home was more important than information about
Yamagata Prefecture, and therefore when we wereinterviewed by the broadcast media later, we proposed to the stations that they air information concerning Fukushima Prefecture, as it was importantto the evacuees.
We received media coverage at the governor’spress conference. We said that there was no difference between FIA doses in Yamagata Prefectureand normal values measured nationwide and that,
although there was no need to be overly concerned,
residents must keep an eye on possible changes in
the future and take appropriate action. (A video of
the interview was made available on the prefectural
government’s website.) The governor later said tous that the press conference reassured residents ofthe prefecture and helped them handle the situation
calmly, making us feel that our visit to Yamagata
was of some help. We were interviewed by reporters on many other occasions. And at such times, we
did our best to describe the situation in the prefecture as plainly and as clearly as possible.
Toward the end of our stay, radioactive contamination of spinach and milk was reported. The staffof the prefectural Department of Agriculture, Forestry and Fisheries asked us about effects of radioactive fallout on agricultural products. As we had
no relevant information, we provided informationthat we obtained from the National Institute for

Norio Takahashi (second from left) and Katsuhisa
Yamasaki (second from right) briefing Yamagata Governor
Mieko Yoshimura (center)

Environmental Sciences and other organizations
after arriving back in Hiroshima. We were told thatthe staff of the department were appreciative of theinformation.
In concluding our report, we would like to pay
our respects to the governor of Yamagata Prefecture, Mieko Yoshimura, and the staff of the prefectural government. We also want to note that wewere deeply impressed by the self-sacrifice anddedication of Mr. Satoh and Mr. Masahide Sudoh,chief of the Public Health and Pharmaceutical
Affairs Section of the prefectural Department of
Health and Welfare, as well as of the public healthnurses at the local health centers. Hang on,
Yamagata! Keep your chin up, Tohoku!

Transition to Exceptional Incorporated Foundation with Councilors
As the preliminary stage for its transition to a
public-interest incorporated foundation, RERF
obtained approval for changes to its Act of Endowment on April 1, 2011, and on April 4 the foundation transitioned to an exceptional foundation with
Councilors by registering as such. The new moniker, however, is strictly for legal purposes, with thefoundation continuing to be referred to by its conventional name of the Radiation Effects Research
Foundation.
As an exceptional foundation with Councilors,
RERF is now equipped with a Board of Councilors,
which serves as the foundation’s decision-making

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body and consists of eight newly appointed Councilors. Without any change in name, the Board of
Directors will serve as RERF’s executive committee, with its three previous Permanent Directors
appointed as Directors. The number of Auditors,
two, remains the same as before.
Aiming at official transition to a public-interest
incorporated foundation in April of next year,
RERF plans to quickly apply for Cabinet Office
approval upon finalizing matters required for thetransition at the meetings of the Board of Directors
and the Board of Councilors in June of this year.

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RERF News

Officials from Fukushima Medical University Visit RERF
On April 25, six officials of Fukushima Medical
University, including Dr. Seiichi Takenoshita, Vice
Chairman of the university, visited RERF’s
Hiroshima Laboratory and were greeted by Dr.
Toshiteru Okubo and other directors, the Associate
Chief of Research, Chief Scientists, and Chief ofSecretariat. Dr. Okubo and Dr. Kazunori Kodama
briefed the visitors at the Auditorium on the forward-looking studies of health effects of radiationthat have been conducted by ABCC-RERF over theyears. The briefing session was followed by a tourof such RERF research departments as the Departments of Clinical Studies, Epidemiology, andInformation Technology. The visitors mentioned
later that it had been very meaningful to see theactual site where studies are being conducted in the
A-bombed city of Hiroshima, as the experiencewould help them establish a system to provide
security and safety for the residents of Fukushima
Prefecture for many years to come, with active discussion between the group and RERF representa-

tives continuing even after the facility tour. The
next day, April 26, they visited the Nagasaki
Laboratory and were briefed by Dr. Masazumi
Akahoshi, Chief of the Department of ClinicalStudies, on the studies conducted in Nagasaki.

Officials from Fukushima Medical University touring RERF
with guidance from Chairman Toshiteru Okubo (left)

Staff News
Kazuo Neriishi, Assistant Chief, Department ofClinical Studies, Hiroshima, retired on December
31, 2010 at the mandatory age and was appointed
Consultant of the department as of January 1, 2011;
he has shared some of his memories of his research
career in Human Interest Notes (see page 30).
Fumiyoshi Kasagi, who remained as AssistantChief, Department of Epidemiology, Hiroshima,
since July 1, 2009 after his mandatory age retirement, resigned on March 31 and joined the Radiation Effects Association in Tokyo on April 1, 2011.
As we reported in the Update last year, Harry
M. Cullings was promoted to the post of Chief ofthe Department of Statistics, effective from April
15, 2010. Likewise, Yoshiaki Kodama and
Yoichiro Kusunoki were promoted to Chief of the
Department of Genetics and Chief of the Department of Radiobiology/Molecular Epidemiology,
respectively, effective from February 1, 2011. With
those promotions, every research department now
has a chief in place, which is expected to further
strengthen the departments and facilitate interdepartmental collaboration. On this occasion, therecently appointed department chiefs were invited
to write about their goals in their new positions.

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Thoughts on Becoming Chief of Statistics
Harry M. Cullings, Chief
Department of Statistics

I was honored to be
asked to take the postof Chief of Statistics
after serving in othercapacities in the department for about ten
years previously. My
goals were naturally to
guide the Statistics
Department in providing the best possible
statistical consulting
service to other departments, and to have theDepartment continue the proud tradition of statistical research at ABCC and RERF that has madesuch a well-known and well-reputed contribution,worldwide, to research on the health effects of ionizing radiation.
As important as methodological developments
have been in the past, there are still great challenges remaining for RERF statisticians. RERF hastremendous stores of data that have not nearly been
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RERF News
completely explored, but they are fraught withproblems such as missing data and measurement
error, like most data from observational studies.
Technology has been adding greatly to the wealthof data by creating measurements on huge numbersof biological variables that can be obtained fromsmall samples from the human body. As statisticians we need to respond to those challenges bylearning new methods and adapting them to theneeds of RERF research, and, when possible, participating in their theoretical and practical development.
I believe that the best single thing I can do as
chief is to encourage communication and provide apleasant and supportive work environment thatencourages learning and productivity. Group thinking as an input to forming approaches to technical(and other) problems has great value, but it requiresthat individuals develop trust and confidence inothers within the department, which the chief must
support and facilitate.
As a statistician, the thing I love most is working on complicated real-world problems and trying
to understand what the data are telling me. I feelgreatly privileged to be able to continue doing
research in areas that interest me in addition toundertaking the responsibilities of being the chief,
and to me this is what really makes it worthwhile towork long hours and think about research problems
at any hour of the day.

30 Years at Hijiyama
Yoshiaki Kodama, Chief
Department of Genetics

My name is Yoshiaki
Kodama, and I recently
became Chief of the
Department of Genetics. I would like torequest your continued support on thisoccasion. I cannot
believe it has been 30
years since I joined
RERF. I previously
lived in Sado, Mito,and Sapporo before moving to Hiroshima, whichmarked my first time living in western Japan. I had
no idea how hot it would be in Hiroshima and wasa little worried about my family before we moved
here as we are resistant to cold but sensitive to heat,
especially after my mentor had scared me by telling me stories about the blazing temperatures. And
he was right! The heat and humidity in the summers of this Seto Inland area was unimaginable for
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someone like me, coming from an area where yourhair often freezes on the way home from a publicbath (in winter, of course). However, people really
do grow accustomed to new circumstances. Led byour children speaking fluent Hiroshima dialect andnot caring at all about the heat, we adapted to life in
Hiroshima, although I have to admit I still get
excited when it snows. Hiroshima has become theplace I have lived the longest in my life.
When I first joined RERF, I found out how
strong the organization’s mission was for investigating A-bomb radiation effects. Even though it
may feel a little uncomfortable to think that everything we do is for the mission, it is quite easy tounderstand as the raison d’être for the researchfoundation. The mission of the Department of
Genetics is to conduct genetic effects research of
A-bomb radiation and biodosimetry studies. Bothstudy areas are time-consuming but important forclarification of late effects of the A-bombings. No
genetic effects have been found thus far despite thevast amount of effort we have made. It is expectedthat a reasonable conclusion regarding this issue
will be obtained on the basis of findings from
DNA-level research to be conducted in the future.
Regardless of the findings we may obtain in the
future, this is research that only RERF can carryout, and we should consider it our responsibility toaccurately assess effects of A-bomb radiation. Even
if we cannot detect genetic effects, we can stilllearn about an upper-bound limit on risk estimates.
I believe we should always keep this in mind as
investigators conducting our research mission.

For Mechanistic Research into
Radiation’s Effects
Yoichiro Kusunoki, Chief, Department ofRadiobiology/Molecular Epidemiology

I have been recently
appointed Chief of the
Department of Radiobiology/Molecular
Epidemiology (RME)
after having served as
Acting Chief for the
past slightly more than
two years. Although I
am still inexperienced
compared with othersenior department chiefs, I am committed to doing
my utmost to pursue radiation effects research. I
look to all of you for your continued guidance andsupport.
The linchpin of the research carried out at the
RME department is to deepen understanding of
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RERF Newsmechanisms behind adverse health effects of radiation. I believe that goal is significant for two reasons. One is that elucidation of such developmental
mechanisms of radiation-associated disease could
lead to creation of effective methods for prevention
and treatment of such disease. The other is thatinvestigation of biomarkers and genotypes related
to disease mechanisms allows application of suchbiomarkers to accurate estimation of disease risk.
Since I joined RERF 25 years ago after leaving
graduate school at the Hiroshima University
Research Institute for Radiation Biology and Medicine (RIRBM), I have been involved in the conductof immunological research. Thanks to the cooperation of many A-bomb survivors and RERF staff, I
have succeeded in accumulating significant
amounts of scientific evidence of changes to theimmune system over long periods caused by radiation. Based on such accumulated data, I am hoping
to proceed with research on radiation-induced
acceleration of immunosenescence and diseaserisk. Molecular analysis of radiation-associatedcancer in our department also requires mechanistic
approaches. To develop and expand on this kind ofresearch, valuable findings accumulated from
RERF’s epidemiological and clinical studies,
stored biosamples, and our high-level statisticalanalysis and information technology capabilities
should be fully utilized. In addition, the latest analysis techniques and research methods must be
introduced to RERF through collaboration with our
Department of Genetics and non-RERF researchersin Japan and abroad. To that end, I would like to
ask for your continued cooperation.
To elucidate the mechanisms involved in
A-bomb radiation effects, and contribute to efforts
toward maintenance of the health of A-bomb survivors. I believe that, for someone born, raised andengaged in research in Hiroshima, this is the best
way to inherit the experiences of Hiroshima andNagasaki and pass that information on to future
generations. I look forward to your continued support.

Awards Received by RERF Scientists
Receiving the IAR Prize
Toshiteru Okubo, Chairman

On February 18, 2011, during the 13th meetingof the World Health Organization’s (WHO) Radiation Emergency Medical Preparedness and Assistance Network (REMPAN), held at Nagasaki University, I presented a lecture as keynote speaker titled“Long-term epidemiological studies of atomicbomb survivors in Hiroshima and Nagasaki: Study
populations, dosimetry, and summary of healtheffects,” which also had been awarded the 10th
International Association of Radiopathology (IAR)
Prize. For this honor, I would like to express myheartfelt appreciation to everyone concerned.
Let me explain the background of my lecture
presentation. Since this year’s REMPAN meeting
was held in Nagasaki, a special session concerning
A-bomb survivor follow-up studies was scheduled.
It was decided at the discretion of Dr. Shunichi
Yamashita, Director-General of the aforementioned
meeting and professor at Nagasaki University, that
RERF would take charge of the relevant session. I
opened the session by outlining A-bomb survivor
follow-up studies, but it should be mentioned that
the IAR Prize was granted not to me as an individual, but to RERF as a whole, and that I received theprize on behalf of RERF as its representative at the
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meeting. Furthermore, it should be said that thetrue awardees were instead Drs. Kazunori Kodama,
Masazumi Akahoshi, Yoshiaki Kodama, andHiroaki Katayama, who followed my lecture with
their own.
The IAR was established in July 1955 as aninternational organization by a French physician,the late Dr. H. Jammet, who had served as a member of the U.S. National Council on Radiation Protection and Measurements (NCRP) in the 1950s.
The association is composed of researchers aroundthe world in the field of radiology. After thepassing of Dr. Jammet, Dr. Shigenobu Nagataki,
former RERF Chairman, served as IAR
Chair, with Dr. Marc
Benderitter from theInstitute de Radioprotection et de Sûreté
Nucléaire (IRSN) of
France recently selected to succeed to therelevant position.
It is my fervent
hope that RERF willcontinue to collaborate with such inter- Certificate from the Internanational organiza- tional Association of Radiopations in the future and thology
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Conference and Workshop Reports
strive to promote fruitful research efforts in the fieldof radiation health effects.

Receiving a Distinguished Service Award
from the Japan Epidemiological
Association
Kazunori Kodama, Chief Scientist

At the 21st Annual Scientific Meeting of theJapan Epidemiological Association held on January 21–22, 2011 in Sapporo, I had the honor ofreceiving a Distinguished Service Award from theJapan Epidemiological Association. Researchers
who have made contributions to progress in epidemiology and development of the Association areawarded the Distinguished Service Award by theJapan Epidemiological Association.
I received the award in recognition for my two
major contributions; organizing the 17th Annual
Scientific Meeting of the Japan Epidemiological
Association held on January 26–27, 2007 inHiroshima and serving as the 6th President of theJapan Epidemiological Association for three years
from January 2007 to January 2010.
During my term of office as President of the

Association, a decision was made by
the government tocompletely revise
the Statistics Act for
the first time in 60
years, which raised
concerns that use of
public statistics byresearchers might
be restricted, becauseof the trend towardtighter protection of Crystal plaque presented by the
personal informa- Japan Epidemiological Association. The Japan Epi- tion
demiological Association took the initiative in making requests to thegovernment, and managed to avoid the problem. It
is essential for us to be able to use public statistics
to conduct the Life Span Study and other studies.
In order to conduct a long-term epidemiologicalstudy in connection with the Fukushima Dai-ichi
nuclear power plant accident, access to public statistics is also essential. In that sense, I may havemade some contributions worthy of a Distinguished Service Award from the Japan Epidemiological Association.

Mini-workshop“Roles of Smoking on Radiation Risk of Lung Cancer”
Nori Nakamura, Chief Scientist
A mini-workshop titled “Roles of smoking onradiation-risk of lung cancer” was held in the
RERF Auditorium on the afternoon of February 4,
2011. The workshop was organized in response to
the proposals by Dr. Michiaki Kai (Oita University
of Nursing and Health Sciences) and Dr. Ohtsura
Niwa (formerly with National Institute of Radiological Sciences). It was motivated by a controversy over possible interpretation of higher risk oflung cancer among smokers with the same radon
concentration, which had resulted from reassessment of radon effects by the International Commission on Radiological Protection (ICRP) in 2009,and by a finding last year (paper by Furukawa etal.) suggesting higher risk of lung cancer attributable to radiation among A-bomb survivors who
smoke (excluding heavy smokers) than among thesurvivors who do not. We also hoped to understandinteractions between radiation and smoking at thecellular (stem cell) level.
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Dr. Okubo’s welcome address was followed by
the presentations “Trends of lung cancer in Japan”
by Dr. Kotaro Ozasa (Chief, Department of Epidemiology), “Joint effects of radiation and smoking
on lung cancer among atomic-bomb survivors” by
Dr. Kyoji Furukawa (Department of Statistics), and“Pilot study: Genetic and epigenetic alterations inlung cancer among atomic bomb survivors” by Dr.
Masataka Taga (Department of Radiobiology/
Molecular Epidemiology). After a short break, thesession resumed and Dr. Yuichi Ishikawa (Cancer
Institute of Japanese Foundation for Cancer
Research) spoke on “Present status of lung cancer
in Japan: Characteristics of Japanese lung cancer
and genotype-phenotype correlations,” Dr. Michiaki
Kai on “Multistage carcinogenesis and lung cancer
risk,” Dr. Suminori Akiba (Kagoshima University)
on “Indoor radon and lung cancer risk,” and Dr.
Charles Land (formerly with U.S. National Cancer
Institute) on “Comments on radiation cancer risk in
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Conference and Workshop Reports
smokers and nonsmokers compared with previous
risk.” The presentations were followed by a general
discussion that concluded the event.
The findings already elucidated are as follows:
1) Non-smokers develop lung cancer, although at
a lower rate. The majority of such lung cancer
is said to be adenocarcinoma occurring in thelung periphery.
2) Earlier, it was mentioned that risks for squamous cell carcinoma (SCC) and small cell carcinoma (SmCC) developing in the central
region of the lungs increase among smokers.
However, adenocarcinoma is recently on theincrease (which is hypothesized as attributable
to improved filters).
3) Not all smoke particles from cigarettes infiltrate
deeply into the lungs.
4) The risk increase from radiation exposure in
SmCC is observed both in A-bomb survivors
and in radon miners (Land’s 1993 paper).
5) Smoking and radiation enhance each other’seffects (synergistic effects).
6) Radon is absorbed into the lungs not only in theform of a gas, but also in the form of solids
attached to atmospheric dust particles. The
range of its α particles is short. Therefore, itwould be difficult to assess which parts of thelung are affected by radon. (If stem cells arelocated several layers of cells deep below thesurface of the respiratory tract, they might not
be exposed to radiation.)

13
carcinoma can be explained by lower radiosensitivity even if radon α particles reach stem cells.
Interactions between radiation and smoking:
Whether exposure to A-bomb radiation or to radon,
effects are greater when radiation and smoking are
combined than when each exerts effects independently (1 + 1 > 2; i.e., joint effects are greater thantheir simple additive effects). However, risk fromsmoking is far greater than that from radiation,
meaning that radiation is not smoking’s equal.
Looking at this from the viewpoint of radiation
effects, although SmCC is not the most prevalent
subtype of lung cancer attributable to smoking, it isstill affected by smoking as its effects are thatmuch stronger. Because radiation and chemicalcompounds in tobacco smoke exert different kindsof damage on DNA and have different cell stimulatory effects, radiation and tobacco smoke probably
complement each other’s weaknesses during themultistage process of carcinogenesis.
At the mini-workshop, I learned that percentages of various lung cancer subtypes differ between
the Japanese and Caucasians and that smoking
effects are smaller among Japanese than among
Westerners. I felt as if I was learning the history ofsmoking in the 20th century in various countries. I
had a great time, seeing Dr. Land after a long time,and engaging in lively discussions. Above all, I
became interested in knowing whether or not thelatest Life Span Study data will support the conclusion made by Dr. Land in his above-mentioned
paper published in 1993, which is now almost 20
years ago (i.e., the lung cancer subtype increasedby radiation exposure is SmCC).
Lastly, I would like to take this opportunity to
express my appreciation to all those who helpedme organize this workshop.

Taking the above points into consideration, I
gave some thought to possible interactions between
smoking and radiation.
A-bomb radiation effects: A-bomb radiation
affected the entire lung uniformly. The lung cancer
subtype that increases with radiation exposure issaid to be SmCC. Therefore, it seems likely that
SmCC is as sensitive toradiation as it is to smoking, and conversely that
SCC and adenocarcinoma
are less sensitive to radiation.
Effects of radon α particles: The lung cancer subtype that is increased byradon exposure is said to be
SmCC, which means that α
particles from radon and its
daughter nuclides reachstem cells, the originating
point of SmCC. The lower
risks for SCC and adeno- Participants of the mini-workshop titled “Roles of smoking on radiation risk of lung cancer”

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RERF Update Volume 22, Issue 1, 2011

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Conference and Workshop Reports

Workshop on Potential Extensions to DS02 Organ Dose Calculations
Harry M. Cullings, Chief, Department of Statistics
One of the notable strengths of RERF’s studies
is their dosimetry—estimation of the radiation
doses received by survivors, without which study
results cannot be stated in terms of risk or effect perunit dose for use in radiation protection. A series of
dosimetry systems for calculating survivors’ doses
based on their detailed location and shielding information have been developed over the last sixty
years by international scientific working groups,
culminating in Dosimetry System DS02. One of
the hallmarks of DS02, and its predecessor DS86,
is that they calculate detailed dose estimates forparticular organs and tissues of the human body,which can differ substantially with an organ’s
effective depth in the body, especially for the dosefrom neutrons. DS02, however, uses the sameorgans and organ dose computational methods as
DS86, which reflect the state of knowledge andcomputing power that were available in the early
1980s. DS86 and DS02 calculate dose only to certain organs, which were chosen in light of theunderstanding of radiation biology in that time
period, and were limited to fifteen organs for practical reasons. For other organs and tissues it has
therefore been necessary to choose surrogates fromamong the 15 organs to provide rough estimates ofdose. Moreover, it has been recognized in recent
years that there has been an explosion of detailed
three-dimensional anatomical data on the humanbody from medical imaging technologies, and thatcomputing power is much greater than it was somethirty years ago.
The above considerations suggested that it
would be useful to explore ways to take advantageof the great effort expended on DS02, by using thedetailed radiation fields that it calculates at individual survivors’ locations, with new organ dose
modules to calculate dose to a wider variety oforgans with improved accuracy. Many of the
aspects of such improved calculations could utilize
resources that are already available in the radiation
protection community, including Monte Carlocomputational packages and methods for developing detailed models of the human body. On February 23 and March 7–8, 2011, the “International
Workshop on Potential Improvements to Organ
Dose Calculation for the Atomic Bomb Survivors
Using DS02” was held at the Hiroshima Laboratory. In addition to two RERF speakers, the workshop included six speakers from four Japanese
research institutes and universities (National Insti-

Return to Table of Contentstute of Radiological Sciences, Japan Atomic Energy
Agency, Kyoto University Reactor Research Institute,and Hiroshima University) and five speakers frominternational agencies and universities (Helmholtz
Institute Munich, Health Canada, Science Applications International Corporation, Oak Ridge National
Laboratories, and Vanderbilt University).
The purpose of the workshop was to discuss
some key needs for improved organ dosimetry andthe practical means by which the organ dose calculations of the DS02 dosimetry system could be
improved. There are a number of organs for which
specific dose estimates are desirable but not currently available. Special meetings were held in connection with the workshop to discuss the technicalissues involved in biodosimetry measurement ofradiation dose using electron spin resonance (ESR)on donated teeth and the need to obtain accurate
DS02 calculations of dose to tooth enamel for comparison to measurements. As DS86 and DS02
include only three models of the human body for
different age categories, there is a need for bettermodeling of the body at various ages during childhood and adolescence. Another need is for gestational age-specific doses for survivors who were
exposed in utero. The workshop ended withfocused discussions of what methodologies, software, and models of the human body should be
used and adapted to the Japanese population of the
1940s, and the participants agreed to collaborate on
developing a new series of models for improved
calculations. Short papers based on the proceedingsof the workshop will be published in a special issueof the journal Radiation Protection Dosimetry.

Workshop on potential extensions to DS02 organ dose calculations held at Hiroshima Laboratory

RERF Update Volume 22, Issue 1, 2011

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Science Articles

Highlights of RERF Departments: Research Activities
in the Department of Epidemiology
Kotaro Ozasa1 and Akihiko Suyama2
Departments of 1Epidemiology (Hiroshima) and 2Epidemiology (Nagasaki), RERF
Abstract
The principal focus of the research program of
the Department of Epidemiology is to study theeffects of ionizing radiation in the Hiroshima andNagasaki survivors of the atomic bombings andtheir children through mortality and cancer incidence studies. Several fixed cohorts—the Life Span
Study (LSS) cohort consisting of about 120,000
A-bomb survivors, the in utero cohort consisting ofabout 3,600 persons who were in utero at the timeof the bombings, and the children of A-bomb survivors (F1) consisting of about 77,000 persons—havebeen established to accomplish the purpose. They
have been followed up for their deaths in all ofJapan and for cancer incidence in Hiroshima andNagasaki. Histological specimens of cancer cases
are also collected by the tissue registries in collaboration with community pathologists. Mail surveys
have been conducted periodically and provided
information on lifestyle and other factors that may
confound or modify the effects of radiation.
Periodic reports of the radiation effects of LSS
mortality and cancer incidence data have beenreleased, and considerable research has been conducted on various aspects of the data and using
additional information from histological diagnoses
and mail surveys. In utero and F1 cohorts have beenstudied as well. The information on the cohort

Research Scientists of Hiroshima Epidemiology (first row
from left) Ritsu Sakata, Hiromi Sugiyama, Kotaro Ozasa(department chief), Yukiko Shimizu, (second row from left)
Eric J. Grant, Truong-Minh Pham, Ayako Takamori (visiting
student fellow)
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members has been provided to all departments of
RERF for their research activities. It is important toharmonize the epidemiological evidence with biological mechanisms of radiation effects. Many
studies in the department have been conducted incollaboration with various researchers inside andoutside RERF. International risk assessment groups
use the cohort study results as the primary basis forradiation risk estimation, such as the U.S. National
Research Council’s Committee on the Biological
Effects of Ionizing Radiation (BEIR VII, 2005), theUnited Nations Scientific Committee on the Effectsof Atomic Radiation (UNSCEAR, 2006), and theInternational Commission on Radiological Protection (ICRP). RERF has vigorously managed theHiroshima and Nagasaki tumor/tissue registries.
The data have long been included in the “Cancer
Incidence in Five Continents” (by the International
Agency for Research on Cancer [IARC]/the International Association of Cancer Registration[IACR]), a compilation of worldwide cancer incidence data, and are given the highest rating by that
consortium.
At the end of 2006, 85% of the LSS cohort
members who were under 10 years old at the timeof the bombing, 89% of in utero, and 90% of the F1cohort were still alive. Therefore, continued follow-up of those young-age groups for an additional
20 years or more is clearly essential. In this article,
recent research activities and future perspectives ofthe department are discussed.

Research Scientists of Nagasaki Epidemiology (from left)
Midori Soda, Akihiko Suyama (department chief)

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Science Articles

Department Staff
The Department of Epidemiology, Hiroshima,currently is comprised of a chief, two associatesenior scientists, one research scientist, one postdoctoral scientist, two visiting scientists, and one
visiting student fellow. The Department of Epidemiology, Nagasaki, includes a chief and one researchscientist.
Research Projects and Recent Progress
1. Life Span Study (LSS)
Evaluation of the late health effects of radiation
derived from the atomic bombs is RERF’s mostimportant goal. It requires unbiased analysis andreporting as well as careful and complete follow-up
of people who survived the atomic bombings. The
LSS cohort consists of a representative populationof survivors in Hiroshima and Nagasaki who havebeen followed up since 1950. Subjects of the study
consist of 93,000 A-bomb survivors who wereselected from a nationwide A-bomb survivors survey conducted in 1950 and 27,000 persons who
were not in Hiroshima or Nagasaki at the time of
the bombings (not-in-city group [NIC]), but who
were residents of either city in 1950. The subjects
were asked about their location, shielding at thetime of the bombings, and other related issues(Master Sample Questionnaire) and individual
doses were subsequently estimated. Dose estimates
are periodically refined. The latest revision of thedosimetry system, DS02, was released in 2003.
The subjects’ survival status is periodicallychecked using the koseki (family registration system) that has virtually complete death ascertainment. The cause of death is obtained from deathcertificates kept at public health centers throughout
Japan. Cancer incidence is available from the cancer registries within Hiroshima and Nagasaki prefectures. Information on leukemia was collectedindependently through a special leukemia registry
kept by area hematologists until 1987. The LSS
cohort also serves as the sampling frame for the
Adult Health Study (AHS) clinical subcohort.
At the end of 2006, 39% of LSS subjects,
including 85% of those exposed before age 10,
were alive, so continued follow-up is essential.
Analyses of interactions between radiation andsmoking will be considered for smoking-related
cancers and for other diseases. Estimation of radiation risks at low-to-moderate dose levels will beconsidered by including lifestyle factors and geographic factors to help interpret the fluctuations ofestimated risk at low-dose levels. Because of highpublic interest, issues of residual A-bomb radiation
exposure will be examined in coordination with the
RERF Dosimetry Committee, although only limited individual information is available.

16
Radiation risk of cancer and non-cancer diseases
Periodic reports of radiation risk on the LSS
have been released along with many more publications on various aspects of the data.1,2 Analyses of
updated cancer and non-cancer mortality data
through 2003 using the DS02 were completed anda manuscript was recently submitted to a scientificjournal. Analyses of specific diseases including
leukemia,3 malignant lymphoma4 (in collaboration
with University of North Carolina), and malignant
tumors in bone and soft tissue 5 have been published. Analyses of mortality from cardiovasculardiseases have been published (Figures 1 and 2)6 andthose for non-cancer respiratory and digestive diseases are being conducted. A study of the bestmodel to fit radiation risk and non-cancer mortality
was completed and a study of influences of comorbidity from cancer and non-cancer diseases on

Radiation dose-response relation (excess relative risk perGy) for death from stroke, showing linear and linear-quadratic functions. Shaded area is 95% confidence region for
fitted linear line. Vertical lines are 95% confidence intervals
for specific dose category risks. Point estimates of risk foreach dose category are indicated by circles.
Figure 1. Radiation risk of stroke (cited from ref. 6)

Radiation dose-response relation (excess relative risk) for
death from heart disease, showing linear and linear-quadratic functions. Shaded area is 95% confidence region for
fitted linear line. Vertical lines are 95% confidence intervals
for specific dose category risks. Point estimates of risk foreach dose category are indicated by circles.
Figure 2. Radiation risk of heart disease (cited from ref. 6)

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RERF Update Volume 22, Issue 1, 2011

Science Articles
the observed radiation effects upon mortality fromvarious diseases is beginning in collaboration with
Kurume University.
Mail surveys and utilization of the data
Mail surveys have been conducted periodically(1965, 69–70, 79–80, and 91–92), which provide
information on lifestyle and other factors that may
confound or modify the effects of radiation. The
following are studies of evaluation of radiation risk
using mail survey data. Many of them were conducted in collaboration with other institutions
including the Radiation Research Partnership (withthe University of Washington and Kurume University) and the University of Rochester.
- Age at menopause was significantly earlier inwomen with high-dose radiation exposures.
- Urothelial cancers showed strong independentassociations with smoking and radiation. No
effect modification or confounding was observedin the radiation effects due to smoking or otherlifestyle factors.
- Potential confounding or interaction of anthropometric factors with radiation on colon cancer
incidence was examined, but there was no evidence that sensitivity to the effects of radiationon colon cancer risk depended on body massindex (BMI).
- The radiation-associated risk of breast cancer
does not vary significantly by reproductive status(menarche and first birth) at the time of thebombings, but is influenced by age at irradiation.
- Esophageal cancer at the lower anatomic segment and cases of diffuse gastric cancer showeda high dose response with radiation. Smoking
was shown to be the most important modifiablerisk factor.7- Chronic renal failure showed a significant association with radiation. Adjustment for selfreported hypertension and diabetes improved themodel fit but did not substantially change theexcess relative risk (ERR) estimate.

17
Population for cancer incidence studies
Since the cohort members in cancer registryareas have not been directly contacted, the numbersof cohort members for cancer incidence studies inthe LSS were estimated using migration information from the AHS subjects by time, age, gender,and city and are now being reviewed and updated
in collaboration with the Department of Statistics.
A similar approach will be necessary for those in
the in utero and F1 cohorts.
Other research topics
Risk of second primary cancers associated withradiation was evaluated in collaboration with the
University of Washington in the Radiation ResearchPartnership. The radiation-related ERRs wereapproximately the same for first and second cancers as illustrated in Figure 3. Radiation dose wasmost strongly related to the risk of solid tumorsthat are considered to be more radiation sensitive,
including second primary lung, colon, female
breast, thyroid, and bladder cancers (Table).8 The
incidence of multiple primary cancers is also being
evaluated in Nagasaki survivors in collaboration
with Nagasaki University. Secondary cancer risk ofa subset from the LSS who had undergone radiotherapy subsequent to A-bomb radiation is being
evaluated in collaboration with the Japan National
Institute of Radiological Sciences. The effects ofsmoking on mortality among the LSS population
have been estimated using methodologies incollaboration with Oxford University because it
has been suggested that the effects of smoking on
mortality in the Japanese population is smaller thanelsewhere.

2. In Utero Cohort Study
The LSS initially did not include those with inutero A-bomb exposure, but since data from theOxford Childhood Cancer Study suggested that the
fetus might be especially sensitive to radiation, it
was decided to study them as a special group. The
in utero cohort was defined on the basis of a roster

A new mail survey
A new survey is required, not only to update theinformation as more than 15 years have passed
since the last mail survey in 1991, but also to collect new information on exposures to radiotherapy
and relatively high-dose diagnostic radiation procedures (e.g., CT scans). In addition, participants inthe clinical health study have been solicitedthrough this mail survey from the LSS subjects
who were younger than 10 years old at the time of
the bombings. As of March 31, 2011, 11,863 subjects responded to the questionnaire.
Figure 3. Radiation risk for first and second cancers (citedfrom ref. 8)
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Table. Relationship between estimated radiation dose and risk of first and second primary cancers(cited from ref. 8)of people born between the day of the bombing and
30 June 1946. Vital status and causes of death forthe 3,600 people in this cohort have been determined through routine, periodic checks of koseki
records using the same procedures as for the LSS.
The most recent cancer incidence paper with larger
numbers of cases suggested a different temporal
pattern of excess between the in utero and younger
LSS cohorts, and that the excess risk following inutero exposure appeared to be somewhat smaller
than that seen in those exposed as children (Figure4).9 Analysis of the mortality data for 1950–2003
has almost been completed.

3. F1 Cohort Study
The purpose of the study is to ascertain the longterm health effects among the children of parents
who were exposed to radiation. A cohort of thechildren of A-bomb survivors (F1) was selectedfrom the children born from May 1946 throughDecember 1984 to parents with a variety ofA-bomb radiation exposures ranging from those
known not to be in the city at the time of the bombing to those who were heavily exposed. The F 1cohort sample consists of 76,814 subjects. The

subjects’ survival status, cause of death, and cancer
incidence have been obtained by the same methods
used for the LSS subjects. Neither cancer incidence
nor cancer or non-cancer mortality was significantly associated with paternal or maternal gonadal
dose10,11 (see also Figure 5). As of the end of 2006,
90% of the F1 cohort were still alive and the average
age was 49.6 years old. Analysis of the mortality
data for 1950–2003 has almost been completed.
F1 mail survey
This survey was primarily designed to ascertain
baseline epidemiological data on the F1 subjects,
and secondarily to identify F1 cohort members willing to participate in clinical health examinations inorder to investigate possible relationships of parental radiation doses to adult-onset diseases in the F1cohort. Among the F 1 cohort, 24,673 members
were selected, whose koseki and current address
were in the AHS catchment areas plus a small number of children of high-dose parents whose koseki
was outside the catchment area but whose current
address was in the catchment area. The survey was
carried out between 2000 and 2006. At the end of
the survey, 16,756 subjects responded. A total of

Figure 4. Solid cancer risk patterns for in utero and childhood exposure in A-bomb survivors (cited from ref. 9)
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To date, the frequencies of cancer and other diseases in theoffspring are unrelated to parental radiation dose, but 20–30
more years of follow-up are needed to provide definitive
evidence (Suyama et al., unpublished).
Figure 5. Relative risk for non-cancer and cancer mortality
in 41,000 offspring of atomic-bomb survivors,
1946–2003

11,951 (71% of questionnaire respondents) actually participated.12 The information of the mail survey data was used as covariates and published in
the report of F1 clinical study analysis, investigating possible associations of parental radiation doseto F1 multifactorial diseases.13

4. Hematological Studies in LSS
The program is designed to document all casesof leukemia, and certain closely-related hematologic diseases like multiple myeloma, lymphoma,
polycythemia vera, myelofibrosis, aplastic anemia,
or myelodysplastic syndrome (MDS). A recent
study examined the radiation risk of MDS in
Nagasaki during 1985–2004 in collaboration with
Nagasaki University and the Statistics Department.
The ERR at 1 Gy was 4.27 (95% confidence interval 1.63–9.48). The MDS risk was significantly
greater among those exposed at younger ages (Figure 6)14 Another study of comprehensive analyses
for leukemia and related diseases is being conducted in collaboration with the Statistics Department.
5. Site-specific Special Cancer Studies in LSS
The tumor and tissue registries of Hiroshima
and Nagasaki prefectures are functioning well andpermit pathologists and epidemiologists to confirm
tissue diagnoses and clinical records and expand
the incidence studies with site-specific surveys,
case-control studies, etc. Certain pathologists at
collaborating hospitals and institutes have worked
extensively with RERF, to maintain uniform protocol and analysis procedures. There are three major
areas of study effort to be undertaken: case ascerReturn to Table of Contents

19tainment, pathological review, and data analysis.
Sources of cancer cases are population-based tumor
and tissue registries in the Hiroshima and Nagasaki
areas, RERF autopsy series, death certificates, sitespecific tumor registries, RERF records gathered in
the past, and others. Information and materials on
possible cases are collected from those sources.
First, the pathologists reviewed the information on
paper and selected probable cases of target cancer(‘the first screening’). For the probable cases, thepathologists may jointly or independently (blindly)
review the materials. If two or more review results
are consistent, they are accepted. If they disagree,
the panel meets jointly to review the cases.
Site-specific special cancer studies have been
conducted for various cancers and/or tumors.
Those studies are conducted in strong collaboration
with the U.S. National Cancer Institute (NCI) andwith the Statistics Department, and also with
Hiroshima and Nagasaki Universities and associated local hospitals. At present, studies for liver,
salivary glands, and central nervous system arecompleted, and are underway for skin, ovary,thyroid, breast, lung, lymphoid system, uterus, andsoft tissue and bone. For examples, a pathology
paper on the characteristics and radiation risk ofpapillary microcarcinoma was published. 15 Forlung cancer, both smoking and radiation exposure
appeared to significantly increase the risk of eachof the major lung cancer histologic types.16

6. Hiroshima and Nagasaki Tumor/Tissue
Registries
Population-based tumor registries have been
active in Hiroshima since 1957 and in Nagasaki
since 1958, and conducted by the methods ofabstracting medical records and notifications from
hospitals and clinics at present. Population-based
tissue registries were established in Hiroshima andNagasaki in 1973 and 1974, respectively. The tis-

Figure 6. Sex- and age-adjusted radiation dose-response
for MDS (cited from ref. 14)

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sue registries are collecting the pathology reports
and representative HE-stained slides of cancer
cases.
The integrated data of tumor and tissue registries have long been included in “Cancer Incidence
in Five Continents” (by IARC/IACR), a compilation of worldwide cancer incidence data, and are
given the highest rating by that consortium. Local
activities of the registries have been reported bydepartment members.17–19

7. Pathology Studies
A Pathology Program has been conducted since
the inception of ABCC. During the early years of
ABCC, it consisted almost entirely of an autopsy
program in the cities of Hiroshima and Nagasaki,with emphasis on the procurement of autopsies of
exposed individuals, but with later modifications toinclude controls and to enhance its epidemiologic
usefulness. It proved extremely useful to verify
mortality information, and it permitted the study ofpossible radiation-induced tissue damage. However, because the autopsy rate declined after the
early 1960s, it was terminated in 1987, and arevised research plan based primarily on surgical
specimens was initiated.
We are taking an inventory of the formalin-fixedparaffin-embedded tissues stored in the Departmentof Epidemiology, which will be computerized tofacilitate future specimen utilization. Those specimens are from around 7,000 autopsies or surgicaloperations. To maintain LSS surgical samples thathave been kept in local hospitals, a new research
project of “Development of an archival system for
surgical cancer samples from A-bomb survivors” isbeing initiated in collaboration with Hiroshima andNagasaki Universities and local hospitals.
Collaborations
The Epidemiology Department collaborates
with the Clinical Studies Department in sharing
data on disease risk factors, mortality data, etc.20
and in conducting the mail surveys that haverecruited subjects for the F1 clinical study and the
expansion of the clinical AHS. It is collaboratingwith the Departments of Genetics and Radiobiology/Molecular Epidemiology for the investigationof pathological specimens of breast and thyroid
cancers, and with the Statistics Department instudy-design and data-analysis efforts. Furthermore, the information on the LSS, in utero, and F1
cohort members has been provided to all depart-20
ments of RERF for their research activities.
The Department of Epidemiology also has anextensive network of outside collaborations,
including multiple collaborative studies with the
U.S. NCI, the Radiation Research Partnership(University of Washington and Kurume University), Oxford University, the National Institute ofRadiological Sciences, Kyushu University, University of Occupational and Environmental Health,and other researchers in various universities. In collaboration with Hiroshima and Nagasaki Universities and local hospitals, pathological programs,
including site-specific cancer studies and storage ofsurgical specimens, are performed. Also we arecollaborating with the Asia Cohort Consortium, aprospective study of numerous combined cohortsthat include over one million Asians to assess theeffects of lifestyle factors on cancer risks.

Future Studies
The major future activities of the department
will be to:
1. Continue to follow-up the LSS, in utero, and F1
cohorts and publish updated estimates of radiation risks for mortality of cancer and noncancer
diseases as well as cancer incidence. Thosestudies will increasingly focus on the LSS subjects who were young at the time of the bombings. Also, covariate data from the LSS mailsurveys will be utilized to evaluate other risk
factors for confounding or modification ofradiation risk.
2. Focus on radiation effects at low-dose levels of
initial radiation exposure, considering sourcesof dose uncertainties, confounding and effectmodification factors such as lifestyles and geographic distribution of the subjects. The indirect A-bomb radiation effects by early entrance
after the explosions and bomb fallout (“blackrain”) will be considered, although limited
information is available.
3. Continue the site-specific cancer studies andthe hematological study with histological/
hematological reviews within the LSS and publish those results.
4. Establish a system to preserve pathological
specimens derived from the LSS, in utero, andF1 cohorts in collaboration with hospitals anduniversities in Hiroshima and Nagasaki areas.
5. Continue the management of the Hiroshima
and Nagasaki tumor/tissue registries in order tosupport the fundamental core studies.

References
1. Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K. Studies of mortality of atomic bomb survivors.
Report 13: Solid cancer and noncancer disease mortality: 1950–1997. Radiat Res 160:381-407, 2003.
2. Preston DL, Ron E, Tokuoka S, Funamoto S, Nishi N, Soda M, Mabuchi K, Kodama K. Solid cancer incidence
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21

in atomic bomb survivors: 1958–98. Radiat Res 168:1-64, 2007.
3. Richardson DB, Sugiyama H, Nishi N, Sakata R, Shimizu Y, Grant EJ, Soda M, Hsu WL, Suyama A, Kodama
K, Kasagi F. Ionizing radiation and leukemia mortality among Japanese atomic bomb survivors, 1950–2000.
Radiat Res 172:368-82, 2009.
4. Richardson DB, Sugiyama H, Wing S, Sakata R, Grant EJ, Shimizu Y, Nishi N, Geyer S, Soda M, Suyama A,
Kasagi F, Kodama K. Positive associations between ionizing radiation and lymphoma mortality among men.
Am J Epidemiol 169:969-76, 2009.
5. Samartzis D, Nishi N, Hayashi M, Cologne JB, Cullings HM, Kodama K, Miles EF, Funamoto S, Suyama A,
Soda M, Kasagi F. Exposure to ionizing radiation and development of bone sarcoma: New insights based on
atomic-bomb survivors of Hiroshima and Nagasaki. J Bone Joint Surg Am 93:1-8, 2011. (doi: 10.2106/
JBJS.J.00256)
6. Shimizu Y, Kodama K, Nishi N, Kasagi F, Suyama A, Soda M, Grant EJ, Sugiyama H, Sakata R, Moriwaki H,
Hayashi M, Konda M, Shore RE. Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki
atomic bomb survivor data, 1950–2003. Br Med J 340:b5349:1-8, 2010.
7. McDougall J, Sakata R, Sugiyama H, Grant EJ, Davis S, Nishi N, Soda M, Shimizu Y, Tatsukawa Y, Kasagi F,
Suyama A, Ross NP, Kopecky KJ, Li CI. Timing of menarche and first birth in relation to risk of breast cancerin A-bomb survivors. Cancer Epidemiol Biomarkers Prev 19:1746-54, 2010.
8. Li CI, Nishi N, McDougall J, Semmens E, Sugiyama H, Soda M, Sakata R, Hayashi M, Kasagi F, Suyama A,
Mabuchi K, Davis S, Kodama K, Kopecky KJ. Relationship between radiation exposure and risk of second
primary cancers among atomic bomb survivors. Cancer Res 70:7187-98, 2010.
9. Preston DL, Cullings HM, Suyama A, Funamoto S, Nishi N, Soda M, Mabuchi K, Kodama K, Kasagi F,
Shore RE. Solid cancer incidence in atomic bomb survivors exposed in utero or as young children. J NatlCancer Inst 100:428-36, 2008.
10. Izumi S, Koyama K, Soda M, Suyama A. Cancer incidence in children and young adults did not increase
relative to parental exposure to atomic bombs. Br J Cancer 89:1709-13, 2003.
11. Izumi S, Suyama A, Koyama K. Radiation-related mortality among offspring of atomic bomb survivors: A
half-century of follow-up. Int J Cancer 107:292-7, 2003.
12. Fujiwara S, Suyama A, Cologne JB, Akahoshi M, Yamada M, Suzuki G, Koyama K, Takahashi N, Kasagi F,
Grant EJ, Lagarde F, Hsu WL, Furukawa K, Ohishi W, Tatsukawa Y, Neriishi K, Takahashi I, Ashizawa K,
Hida A, Imaizumi M, Nagano J, Cullings HM, Katayama H, Ross NP, Kodama K, Shore RE. Prevalence ofadult-onset multifactorial disease among offspring of atomic bomb survivors. Radiat Res 170:451-7, 2008.
13. Suyama A, Izumi S, Koyama K, Sakata R, Nishi N, Soda M, Grant EJ, Shimizu Y, Furukawa K, Cullings HM,
Kasagi F, Kodama K. The offspring of atomic bomb survivors: Cancer and non-cancer mortality and cancer
incidence. Nakashima M, Takamura N, Tsukasaki K, Nagayama Y, Yamashita S, eds. Radiation Health Risk
Sciences. Proceedings of the First International Symposium of the Nagasaki University Global COE Program“Global Strategic Center for Radiation Health Risk Control” 2008. Tokyo, Japan: Springer; 2009, pp 57-62.
14. Iwanaga M, Hsu WL, Soda M, Tasaki Y, Tawara M, Joh T, Momita S, Amenomori T, Yamamura M, Tsutsumi
C, Yoshida Y, Koba T, Kawaguchi Y, Miyazaki Y, Matsuo T, Preston DL, Suyama A, Kodama K, Tomonaga
M. Risk of myelodysplastic syndromes in people exposed to ionizing radiation: A retrospective cohort studyof Nagasaki atomic bomb survivors. J Clin Oncol, 2010. (doi: 10.1200/JCO.2010.31.3080)
15. Hayashi Y, Lagarde F, Tsuda N, Funamoto S, Preston DL, Koyama K, Mabuchi K, Ron E, Kodama K,
Tokuoka S. Papillary microcarcinoma of the thyroid among atomic bomb survivors: Tumor characteristics
and radiation risk. Cancer 116:1646-55, 2010.
16. Furukawa K, Preston DL, Lönn S, Funamoto S, Yonehara S, Matsuo T, Egawa H, Tokuoka S, Ozasa K,
Kasagi F, Kodama K, Mabuchi K. Radiation and smoking effects on lung cancer incidence among atomicbomb survivors. Radiat Res 174:72-82, 2010.
17. Sugiyama H, Nishi N, Kuwabara M, Ninomiya M, Arita K, Yasui W, Kasagi F, Kodama K. Incidence andsurvival of childhood cancer cases diagnosed between 1998 and 2000 in Hiroshima City, Japan. Asian Pac J
Cancer Prev 10:675-80, 2009.
18. Sugiyama H, Nishi N, Ito K, Narahara H, Yasui W, Kajihara H, Kamada N, Arita K, Ozasa K. Achievementsof follow-back survey of the Hiroshima Cancer Registry. Hiroshima Igaku [J Hiroshima Med Assoc] 62:52832, 2009. (Japanese)
19. Suyama A, Soda M. The current status of cancer registries in Nagasaki Prefecture. JACR Monogr 14:35-8,
2009. (Japanese)
20. Kasagi F, Yamada M, Sasaki H, Fujita S. Biological score and mortality based on a 30-year mortality
follow-up: Radiation Effects Research Foundation Adult Health Study. J Gerontol A Biol Sci Med Sci
64A:865-70, 2009.
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Highlights of RERF Departments: Research
Activities in the Department of Statistics
Harry M. Cullings
Department of Statistics, RERF
Abstract
The Statistics Department develops and implements methods for radiation risk estimation andprovides statistical consulting support to RERF
researchers in study design, data quality assurance,and data analysis. In addition, the department
implements a dosimetry system for calculating survivors’ radiation doses and maintains a database ofsurvivor dose estimates, presently using the DS02
system provided by a combined external and internal scientific working group, and provides key statistical and dosimetric support to RERF projects inbiodosimetry. The department’s research activities
relate to the selection and adaptation of appropriate
biostatistical methods, or development of new
methods, and their application to RERF’s epidemiological, clinical, and basic sciences data.
The Statistics Department has historically led in
the development of analytical methods for major
aspects of the RERF research program such as risk
estimation. This includes not only the developmentof tools such as Poisson regression but methods tohandle various problem areas in follow-up data ofmajor RERF cohorts, such as dose uncertainty,
undocumented out-migration of cohort members
from cancer tumor registry catchment areas, andmissing data on smoking and other potentially confounding risk factors apart from the radiation doses
received directly from the atomic bombs. The
department also develops methods for analysis of
longitudinal data from the Adult Health Study,1which involve repeated measurements on the same
individuals over time, with inevitable changes inlaboratory methods, instrumentation, and the items
being measured that correspond to changes inmedical science and technology.
The valuable and limited nature of RERF’s biosample resources leads to special requirements for
related studies. Researchers in Statistics evaluate
and develop special methods of sub-cohort sampling for various special clinical studies, such as
nested case-control studies of cancer, radiation
effect modification using serum biomarkers, ormolecular epidemiology studies of the immunogenome and cancer susceptibility in response to radiation. Statisticians also develop many special methods to meet the requirements of RERF’s basic
Return to Table of Contentsscience research in genetics, immunology, radiation biology, and molecular epidemiology. This
increasingly requires methods for analysis of highdimensional data being generated by technologies
such as microarrays that provide large numbers ofmeasurements on a single sample.
Dosimetry is an active area of research at RERF,
and the Statistics Department collaborates actively
with researchers in the Epidemiology Department
on the improvement of survivors’ exposure data
and the evaluation of potential individual and population exposure from residual radiation after thebombings, and with researchers in the Genetics
Department on the important data from biodosimetry such as chromosome aberration analyses andelectron spin resonance analyses of teeth.
Unlike other departments, the Statistics Department provides structured and extensive consulting
services to other departments, in addition to doing
its own research. Given the crucial importance ofsound statistical advice in the design, analysis, andconduct of studies, the department tries to take aproactive approach to consulting, beginning withearly involvement in study design, and devotes amajority of its staff’s effort to consulting.

Department Staff
The Statistics Department currently comprises
the chief, assistant chief, two senior scientists, anassociate senior scientist, three research scientists, two
research assistants, and an administrative assistant.

Research Scientists of Statistics (first row from left) Kyoji
Furukawa, John B. Cologne, Harry M. Cullings (department
chief), Eiji Nakashima (second row from left) Munechika
Misumi, Robert D. Abbott, Ravindra Khattree, Wan-Ling Hsu

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Research Areas
Risk Estimation Methodology
A major focus of the department’s research inmethods of risk assessment is the use of individual
data, which allows advantages over use of groupeddata as are used in methods such as Poisson regression. Potential advantages include improved ability
to incorporate mechanistic hypotheses, model
missing-data mechanisms, examine the shape ofthe dose response, and account for uncertainties indose estimates. Those advantages come at a cost:
the need to evaluate integrals of complicated likelihood functions such as those of Bayesian models
provides a computational challenge due to thesheer number of calculations involved in methods
such as Markov Chain Monte Carlo (MCMC)
approximations, that has not yet been overcome formost of the data sets of interest. As part of aninterim solution to the particular problem of missing data, research has been initiated on the technique of multiple imputation, and a manuscript has
been prepared on its use for missing smoking datain risk estimation of radiation and lung cancer.
The department continues to collaborate withinvestigators at the U.S. National Cancer Institute
Radiation Effects Branch, resulting in three published papers this past year and involvement inseveral new research projects. A recent paper fromthis collaboration involves the application of generalized additive and multiplicative risk models tomore fully investigate the interaction between
smoking and radiation in development of lung cancer (Figure 1).2
Another area of interest is the radiobiologicaleffectiveness (RBE) of neutrons. This is motivatedby recurring concerns about how neutron doseshould be treated, i.e., by particular weighting, in
RERF’s major studies, as well as other fundamental concerns in radiation biology. The department
recently began collaborating with a senior former
RERF investigator and plans a manuscript on the

results of attempting to estimate an optimal weightfor neutron dose in risk regression using RERF
cancer mortality data.
Another avenue of basic statistical research
related to the use of individual data concerns methods for studies in which outcomes such as cancer
are treated as survival (time to event) type data andanalyzed by Cox regression. A member of thedepartment performed research on choice of timescales, i.e., age vs. time since study inception, in
Cox regression of epidemiologic follow-up data,and presented methods and recommendations in an
RERF colloquium. The department also collaborated with investigators at the National Taiwan
University to create a statistical research protocol(RP) to test a new semi-parametric survival extrapolation model using RERF data.
Finally, geospatial methods can play an important role in RERF studies. They can check in detailthe usual assumptions of spatial uniformity, acrossthe study area, of baseline rates of the health outcomes under study, providing a basis for hypotheses that can be investigated further in regard tocauses of any patterns that are found. Such investigations can address concerns being raised by external investigators about putative sources of undocumented exposure to residual radiation. They arealso highly relevant to emerging concerns about theability to quantify “low dose” risk. A manuscripton geospatial analysis of cancer incidence in theLife Span Study has been prepared 3 and an RP andother manuscripts are being planned.
Causal Models
Causal models apply to situations in which ameasurable risk factor is thought to lie on a causal
pathway between 1) radiation and other “exogenous” risk factors and 2) the health outcome ofinterest. The department has collaborated with
Kurume University in developing an RP on causal
modeling applied to radiation, inflammation, andFigure 1. Radiation risk of lung cancer for different levels of smoking
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24

cataracts, and is more generally interested in finding ways to address the question of intermediaterisk factors. The department recently had a newstatistical RP approved on specialized methods ofintermediate risk factor analysis for stratified(counter-matched) nested case-control sampling
designs used in RERF studies. (This also relates tothe next topic of special study designs.)

expansion of cells in intermediate stages. The
department continued to support a collaborative
research project on modeling of leukemia withinvestigators from RIVM, with a manuscript in
preparation, and collaborated on a manuscript on
mechanistic vs. descriptive modeling of solid cancer and multi-model inference with investigatorsfrom HIM.5

Special Sub-cohort and Two-stage Study Designs
In addition to the causal modeling just mentioned, other aspects of sub-cohort designs arebeing actively researched. Recent work has
included an evaluation of statistical efficiency vs.
sub-cohort sampling fraction for case-cohort
designs (Figure 2), and the need in such studies tothink of them as two-stage studies and correct forthe distribution in the sub-sample of variables thatare known only in the sub-sample, using information from their relationship to variables that are
known for the full cohort, which was presented at
an RERF colloquium. Members of the department
also produced an S-plus (statistical software) program to perform the “swapper” algorithm for stratified case-cohort data (such as those collected in theradiobiology/molecular epidemiology study of
immunogenes and cancer) as a springboard toward
eventually writing an R function to add to the publicly available (freeware) R package for survival
analysis, which lacks this needed capability due tothe algorithmic complexity.

Dosimetric Uncertainty
The problem of uncertainty in the dose estimates of survivors has been a statistical problem ofconcern for many years at ABCC and RERF.6,7 The
Statistics Department has continued to actively collaborate with a former investigator who mademajor contributions to theory and methodology on
the adjustment of dose estimates to correct for theeffect of dose error under an assumed error model,8with the collaboration focusing most recently on
treatments that distinguish different types of error 9
and possibly different classes of survivors with different error distributions, and simulations to determine the effect on risk estimation of detailed statistical assumptions about errors in dose. In addition,
the department has entered into several new collaborations with external investigators who areinterested in using biodosimetry data to develop
information on dose uncertainty. In the last year, acompleted RP and an external funding award fromthe U.S. National Institute of Health have beenachieved by one of the groups from the Fred
Hutchinson Cancer Research Center in Seattle,
Washington, for a semi-parametric approach withminimal assumptions about the statistical form of
the dose uncertainty, using partial (on part of thecohort) biodosimetry data. Another RP is nearing
completion, with a group from the University of
Buffalo in New York, on an instrumental variables
approach to dose error that utilizes a more explicit
statistical error model. Finally, a new RP is inpreparation with a group from the University ofSouthern California, on joint modeling of radiationdose estimates, chromosomal aberrations, andearly (e.g., epilation) as well as late (e.g., cancer)
effects of radiation. (The latter project also relates
to the previous item on causal modeling, and all of
the three new external collaborations just mentioned relate to the next item: biodosimetry.)

Mechanistic Modeling of Carcinogenesis
The Statistics Department has ongoing collaborations with external investigators interested inmechanistic modeling of carcinogenesis and leukemogenesis, at the Dutch radiation protection institute (RIVM) and at the Helmholtz Institute in
Munich (HIM), Germany.4 Both groups are interested in two-stage type models that allow for clonal

Figure 2. Effect of sub-cohort fraction in case-cohort
designs
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Biodosimetry
In addition to being interesting in their own
right, biodosimetry results have great value in evaluating the uncertainty in survivor dose estimatesfrom the dosimetry systems (i.e., DS02), which are
based on reported information about survivors’
location and shielding at the time of the bombings.
While the biodosimetry results have considerable
uncertainty of their own, their errors are not
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thought to be correlated with the errors in the survivors’ dose estimates. The Statistics Department
provides detailed DS02 dose estimates and otherrelated data as well as statistical analysis for all of
the biodosimetry efforts. For chromosomal aberrations, for which Genetics researchers have been
accumulating results using fluorescent in situ
hybridization (FISH), Statistics has provided initial
dose-effect estimates using specialized regression
models for data that are considered to be over-disperse Poisson rather than over-disperse binomiallydistributed, 10 due to the difference in scoring
method for FISH vs. conventional Giemsa staining,
and will continue to do so. (By “over-disperse,” wemean that when, for example, the chromosomal
aberration results are regressed on the survivors’
dose estimates, one sees a scatter about the regression line that is much larger than expected from thebinomial or Poisson “sampling error” due to thelimited number of cells that are scored for eachindividual.)
Statistics also supports electron spin resonance(ESR) measurements of gamma dose in the enamelof donated teeth, which is the subject of a recent
manuscript 11 by investigators in Genetics, withanother manuscript in preparation, and a new international collaboration between Genetics investigators and a measurement laboratory at HIM,
Germany. Support was also given to measurements
by the new technique of accelerator mass spectroscopic measurements of the isotope 41Ca in tooth
enamel, as a measure of exposure to thermal neutrons, which were done by Genetics investigators incollaboration with HIM.12
Dosimetry
The Statistics Department provides ongoingsupport to the Dosimetry Committee’s efforts toimprove survivor location estimates by using mosaics of geometrically corrected pre-bombing aerial
photographs of Hiroshima and Nagasaki to achieve
two major goals. One is to remove local distortionsin the 1945 U.S. Army maps by “rubber sheeting”
them to the photographic mosaics and provide corresponding mathematical transformations fromgrid coordinates of the U.S. Army maps to contemporary geographical coordinates. The second is to
use the photographic mosaics to directly locate, incontemporary geographical coordinates, the neighborhood drawings of survivors with shielding histories, by linking the streets and buildings depictedon the drawings to the same objects on the photographic mosaics.
The department also participates actively inefforts to evaluate potential doses that members of
RERF cohorts may have received from residual
radiation. This involves a number of efforts, starting with using survivor location information to
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25
make estimates of cumulative dose from fallout inknown areas of fallout in both cities. Members of
Statistics also participate in external collaborative
research groups attempting to elucidate whether
there is any evidence of undocumented fallout inareas of Hiroshima other than the known, small
area in Koi-Takasu about 3 km west of the hypocenter. Recent efforts in this regard include twopresentations, an interim report 13 and a book chapter (under review) on geospatial analysis of the
fallout isotope 137Cs measured by external investigators in Hiroshima soil samples. The department
also plans collaborative work with Epidemiology
to evaluate the population dose potentially associated with early entry into the cities due to gamma
ray exposure from neutron-activated soils near the
hypocenters.
Statistics organized and hosted an international
workshop in March 2011 on ways to improve andextend DS02 organ dosimetry by using DS02’s
existing calculations of the energy and directional
distributions of neutrons and gamma rays inshielded locations occupied by survivors. They
would be combined with new computational methods and models of the human body from contemporary medical imaging technology to obtain better
calculations of body self-shielding. There are anumber of organs for which specific dose estimates
are desirable but not currently available, such as theheart, kidney, and thymus, as well as teeth. Special
meetings were held in connection with the workshop to discuss the technical issues involved inbiodosimetry measurement of radiation dose using
ESR on donated teeth and the need to obtain accurate DS02 calculations of dose to tooth enamel forcomparison to measurements, which relates to theitem on Biodosimetry above. Of particular note isthat, as DS86 and DS02 include only three modelsof the human body for different age categories,
there is a need for better modeling of the body at
various ages during childhood and adolescence.
Another need is for gestational age-specific doses
for survivors who were exposed in utero.
Bioinformatics
Although members of the department are notdoing research in bioinformatics as yet, Statistics
recently organized and led two in-house workshops
on related topics (one an overview, the second
focusing on microarray and genome-wide association studies) and prepared for additional sessions
on multiple testing (false discovery rate) and methods for association analysis with haplotype (phase)
estimation. This workshop approach is expected tocontinue as needs increase for analytical methods
suited to high-dimensional data, linkage to external
knowledge bases, interdisciplinary integration ofknowledge in a systems biology paradigm, etc.
RERF Update Volume 22, Issue 1, 2011

Science Articles

Future Plans
The Statistics Department will continue its primary role of statistical consulting and oversight onmost of the research projects conducted at RERF.
This will involve design and statistical power considerations and culminate with the analysis andinterpretation of the data. The department alsoplans to increase its role in providing statisticaleducation to other researchers. The department will
become more involved with other departments andthe Information Technology Department in developing policies and procedures for data archiving
and quality assessment.14 Statistics will also continue to implement the dosimetry systems andmaintain related databases. Related to the new DataManagement and Documentation Committee, thedepartment intends in the next five years to implement (within the Statistics Department) methods
for effective documentation, storage, and retrievalof analytical datasets and scripts (detailed command logs of mathematical and statistical operations performed in preparing and analyzing thedata). However, members of the department will
also continue to conduct research on statisticalproblems related to issues encountered with RERF
data in a number of areas.
Researchers in the Statistics Department hope toovercome computational problems in the use ofBayesian methods, especially with individual data,
to: incorporate mechanistic hypotheses and family
relationships (possible clustering in terms of radiation sensitivity); model missing-data mechanisms(e.g., for mail-survey data); develop flexible methods of making inference about the shape of thedose response (especially the low-dose response);
and utilize more flexible and detailed error models
to account for uncertainties in dose estimates.
Also, radiation risk assessment has generally
been performed assuming that various causes ofdeath are independent of each other, and this may
not be true. Statistical methods for risk assessments
will be examined or developed to deal with thosedependencies, which would become an increasingproblem at older ages when the overall force ofmortality is greater.
Another focus is to further develop methods toperform analyses involving intermediate (mediating) factors, a common problem in epidemiologic
and clinical datasets that is often not adequately
considered. Methods for the analysis of joint radiation and other risk-factor effects involving potential
mediation effects in complex models of risk prediction are expected to be worked out within the next
two or three years. Plans are being made to explore
methods and models used for estimating probability of radiation causation of adverse outcomes withjoint risk-factor exposure and incorporating measurement uncertainties. Work will be done to conReturn to Table of Contents

26
sider how to translate risk estimates from complex
causal models into conditional probability of causation estimates by apportioning causation between
direct and mediated pathways.15
The basic science departments are increasingly
generating data with numerous endpoints (e.g.,
microarrays, genome-wide scans). Such “highdimensional data,” in which the number of measured
variables is often much larger than the number ofsamples measured (p>>n), require special methods
to control for multiple testing (false discovery rates)and deal with computational issues for large numbers of covariates, many of which are correlated.
Statistical and quantitative methods such as forms ofregularized regression, Bayesian network analysis,
etc., are rapidly evolving in this area. Some members of the department have gained expertise withsome of the bioinformatics packages, and thedepartment plans to continue developing expertisein this area, and in bioinformatics more generally, toapply new state-of-the-art methods to such data.
There is also often a need to analyze and evaluate the uncertainty (misclassification rates or standard errors) in lab results and other covariates used
as independent variables in RERF studies, and toevaluate or correct for their effects on study results,
particularly where there is no “gold standard”
result available to validate an assay.16 Examples ofuseful approaches might include the use of finite
mixture models to model a set of lab results, theinclusion of random effects in a regression, or asimple analysis of the sensitivity of the results of astudy to a given size of error in a key variable.
Plans will be developed to improve the level ofrigor in selecting or developing such methods andapplying them when appropriate.
Finally, various aspects of research into dosimetry are expected to continue, including dose uncertainty and improved methods of dose estimation.
Although dosimetry system DS02 provides definitive distance- and shielding-specific data on numbers of gamma rays and neutrons classified byenergy and direction (fluences), recent developments of voxel phantoms have made it clear thatDS02’s methods of using these fluences in organdose calculation can be improved and extended.
This could involve both new Monte Carlo methods
and better models of the human body emerging
from medical imaging technologies, and could provide better and more extensive (e.g., to heart, fetus,
and teeth) organ dose estimates. It could also provide dose estimates related to partial body exposures such as those of Nagasaki factory workers
who were behind benches or other heavy equipment. The results of the recent international workshop will be used to create a scope of work for a
project that can be implemented within the next
three to four years.
RERF Update Volume 22, Issue 1, 2011

Science Articles

27

References
1. Hsu WL, Tatsukawa Y, Neriishi K, Yamada M, Cologne JB, Fujiwara S: Longitudinal trends of total whiteblood cell and differential white blood cell counts of atomic bomb survivors. J Radiat Res 51:431-9, 2010.
2. Furukawa K, Preston D, Lönn S, Funamoto S, Yonehara S, Matsuo T, Egawa H, Tokuoka S, Ozasa K, Kasagi
F, Kodama K, Mabuchi K: Radiation and smoking effects on lung cancer incidence among atomic-bomb
survivors. Radiat Res 174:72-82, 2010.
3. Cullings HM, Grant EJ, Joshi S, Patil GP: Application of geospatial hotspotting to cancer incidence data for
the Japanese atomic bomb survivors. (submitted)
4. Heidenreich WF, Cullings HM: Use of the individual data of the A-bomb survivors for biologically based
cancer models. Radiat Environ Biophys 49(1):39-46, 2010.
5. Kaiser JC, Jacob P, Meckback R, Cullings HM: Breast cancer risk in atomic bomb survivors from multimodel
inference with incidence data 1958–1998. (submitted)
6. Jablon S: Atomic bomb radiation dose estimation at ABCC. ABCC Technical Report 23-71. Hiroshima andNagasaki, Japan: Atomic Bomb Casualty Commission; 1971.
7. Gilbert ES: Some effects of random dose measurement errors on analyses of atomic bomb survivor data.
Radiat Res 98:591-605, 1984.
8. Pierce DA, Stram DO, Vaeth M: Allowing for random errors in radiation dose estimates for the atomic bomb
survivor data. Radiat Res 123(3):275-84, 1989.
9. Pierce DA, Vaeth M, Cologne JB: Allowance for random dose estimation errors in atomic bomb survivor
studies: A revision. Radiat Res 170(1):118-26, 2008.
10. Stram DO, Sposto R, Preston D, Abrahamson S, Honda T, Awa AA: Stable chromosome aberrations among
A-bomb survivors: An update. Radiat Res 136(1):29-36, 1993.
11. Hirai Y, Kodama Y, Cullings HM, Miyazawa C, Nakamura N: Electron spin resonance analysis of tooth
enamel provides no evidence for exposures to large radiation doses in distally-exposed A-bomb survivors.
(submitted)
12. Rühm W, Wallner A, Cullings HM, Egbert SD, El-Faramawy N, Faestermann T, Kaul DC, Knie K, Korschinek
G, Nakamura N, Roberts JA, Rugel G: 41Ca in tooth enamel. Part II: A means for retrospective biologicalneutron dosimetry in atomic bomb survivors. Radiat Res 174(1):146-54, 2010.
13. Cullings HM: A preliminary geospatial analysis of 137Cs measured in soil cores from Hiroshima. Researchgroup on the black-rain fallout of the Hiroshima A-bomb, ed. Current Status of Studies on Radioactive Fallout
with “Black-rain” Due to the Hiroshima Atomic Bomb. Interim report of research group on the black-rain
fallout of the Hiroshima A-bomb. 2010, pp 119-33 (Proceedings of workshop on black rain of the Hiroshima
atomic bomb and related studies, Hiroshima, 3–4 March 2010).
14. Cologne JB, Grant EJ, Nakashima E, Funamoto S, Katayama H: Protecting privacy in shared epidemiologic
data without compromising analysis potential. (submitted)
15. Cologne JB, Cullings HM, Furukawa K, Ross NP: Attributable risk for radiation in the presence of other risk
factors. Health Physics 99:603-12, 2010.
16. Nakashima E, Fujii Y, Neriishi K, Minamoto A: Assessment of misclassification in a binary response:
Recovering information on clinically significant cataract prevalence from cataract surgery data in atomicbomb survivors. (submitted)

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RERF Update Volume 22, Issue 1, 2011

28

Human Interest Notes

In the Beginning
William J. Schull, Former Vice Chairmam
As one gazes across today’s Hiroshima it is nighimpossible to envisage the appearance of the city in1947 when the ABCC (Atomic Bomb Casualty
Commission) came into existence. The core of thecity, which had been literally obliterated, was apatchwork of hastily constructed houses and placesof business amidst which was dispersed a few renovated ferro-concrete structures that had withstood
the atomic bomb’s blast, such as the Nisseki Byoin
and the Bank of Yamaguchi. The Heiwa dori, thenknown as the Hyaku meter dori, was a grasslessand treeless slab of parched earth 300 feet wide,
dividing the northern part of the city from thesouthern. Intracity transportation was a test in persistence and courage. There was the occasionaltrolley or bus (often charcoal burning) or bata-batataxi or a bicycle for the intrepid. The simple act ofmoving from the eastern to the western portion of
the city was a frustrating experience made so by thedestruction or damage of so many of the city’s
bridges, and the devious route one had to use as aconsequence. The lovely riverside parks that now
line the Kyobashi-gawa were end-to-end shanties
then. There was no cenotaph nor was there a suitable memorial to the thousands whose lives weresnuffed in seconds on that fateful August day.
The economic situation was desperate. Food was
scarce. Housing was limited. Employment opportunities were few since much of Hiroshima’s heavy
industry had been devoted to the war effort and in
the postwar years was very slow to recover. Matterswere made worse by the forceable repatriation ofseven million Japanese from Korea, Manchuria, andsoutheast Asia in the first years following the cessation of hostilities. When those repatriates arrived inJapan they were filtered through relocation centerswhere they were DDTed, their health assessed for
infectious disease, and then assigned to a resettlement area. It was the practice to settle them in theareas where they or their ancestors had lived prior totheir migration from Japan. As a consequence of thispolicy, since Hiroshima and Yamaguchi prefectures
have long been fertile regions for the recruitment of
migrants, these two prefectures received a disproportionate number of the returnees. One of the relocation centers was on Ninoshima, and it continued
to operate until the peace treaty was signed in 1951.
This was where the Commission was born andwould function. It was six thousand miles from the
National Academy of Science’s National ResearchCouncil, its oversight organization. Despite thisdistance, it had to establish a research program that
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addressed all of society’s concerns about the new
threat posed by nuclear weaponry and ionizing
radiation. There was no paradigm, no model that
the Commission could emulate. It would sink orswim on the basis of its own perceptiveness andingenuity. This was a challenge which under thefreest of circumstances would be formidable, but
the Commission was not free. It existed through thesufferance of the Occupation, on whom its material
needs depended, and the cooperation of the survivors whose participation was central to the organization’s very existence. The immediate issues,
however, were staffing and logistics. An openended research program requires an open-ended
capacity to recruit. But this did not exist. It wascompromised by distance, nationality, and skill
needs. Those barriers notwithstanding, within three
years the Commission had a thousand employees.
Such rapid growth brings its own problems which
often involve the maintenance of a common senseof purpose and goals, but there were other complications unique to the time and location of the Commission’s research activities. Nagasaki fell within
the purview of the American Occupation Forceswhereas Hiroshima was British CommonwealthOccupation Forces territory. In most matters thisfact meant little; it was only in housing and accessto some aspects of shopping where the Australian
government’s white-only policy was restrictive.
Construction of the buildings that now house theFoundation began with a formal Shinto groundbreaking ceremony in July 1949. Most of the work
was completed by the end of 1950 when the genetics unit in the Red Cross Hospital and the clinicaland administrative offices that had been in Ujina
were moved to Hijiyama. Almost immediately
thereafter construction was begun on the building
now known as Hijiyama Hall. The latter would beoccupied in late 1953. Prior to the completion of

ABCC’s Ujina clinic used prior to move to new Hijiyama
facilities in 1950

RERF Update Volume 22, Issue 1, 2011

Human Interest Notes
this building the bulk of the foreign staff lived incommandeered or newly constructed housing inKure, Nijimura, and North Camp. The daily drivefrom these quarters to Hiroshima was tedious andtook most of an hour. To some extent, the tedium
was broken by the fishing and farming activities wesaw to left and right, but after weeks even this paled.
That situation would persist until 1959 when enoughleasable housing became available in Hiroshima tounite all of the foreign staff. Our colleagues in
Nagasaki never faced the separation that occurredin the Hiroshima area. Enough of the city had survived the bombing to provide housing for ABCC’s
staff.
Each of those formative years had its own bookmarks. For example, 1950 was a particularly unsettling year for the Commission and its staff for two
reasons. First, the Korean war began in June of thatyear, and at least initially it was not clear what
effect this would have on our fledgling research
institution. We would learn that the needs of theforces in Korea did not impinge significantly on
our logistic needs. Fuel continued to be available
for our vehicles as did ample food. The second, theother signal event of the year, arose as a consequence of a disagreement between the Atomic
Energy Commission and the National ResearchCouncil on the management and cost of the studies.
A small committee was dispatched to Japan toassess the progress of the studies then underway
and to ascertain whether the requisite quality could
be maintained on a smaller budget. That committee
recommended closure of the research effort. They
based their decision on the absence of evidence ofsignificant health effects (and at the time of theirvisit this was true), and the doubt that quality could
be maintained on a sharply restricted budget. Fortunately, wiser counsel intervened and this recommendation was never implemented. However, it did
have a disquieting effect upon the staff who learned
that they were vulnerable to capricious decisions
by “authorities” either uninterested in what was
being achieved or had other agendas.
Most of us comprising the American staff in theearly years served the Commission on two-year
contracts that we presumed were renewable withgood performance. But relatively few of theyounger scientific staff actually ever renewed(myself included). This was not due to dissatisfaction with our duties in Japan, but rather our career
aspirations. Those of us set on an academic careersoon recognized that we were in a tenuous position
insofar as recruitment to a university position wasconcerned. First, we were far removed from theactive job market place, and were often unaware ofa job opening until it had been filled. And, second,
the recency of the initiation of most of the research
projects and our involvement largely with design
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29
aspects meant that there was as yet no data of consequence available to publish. Given the importance of publications to the young aspirant academician, that was a serious problem. Senior staff whocame to Japan on leave of absence from a university position did not share our concerns. This is ofcourse a far cry from the situation that now prevails
where lifetime employment seems to be the rule.
But life is not made up of only large decisions—
there are many minor ones. The latter are more idiosyncratic generally and these affect different persons
in different ways. I can only cite (by way of illustration) some of the ones that affected me. Both of myconcerns will seem trivial in hindsight and perhaps
they were, but some situations in life must be personally experienced to be a fair judge of the concerns ofothers. Since the Genetics Office was in the Hiroshima
Red Cross Hospital and not with the central offices of
the Commission, lunch was a daily challenge. I had
two options—either to return to Ujina and the dining
facility the Commission maintained there or visit theAustralian forces canteen in the building housing the
Fukuya Department Store. Whichever my choice, thedrive shared a common peril, a swerving vehicle trying to avoid a car-swallowing pit in the road or an
unsteady aged cyclist. Every new employee soon recognized that Japan is such a scenically beautiful
country that a camera is a “must.” While few goodcameras were available on the Japanese market, thepost exchange easily filled our need. There were
Leicas, Contaxes, Exactas, Rolliflexes, and two
new Japanese cameras, the Canon and the Nikon,that would quickly establish themselves as worthy
competitors to their German counterparts.
My involvement in the studies in Japan extend
over sixty years, and through that involvement I
have achieved scientific maturity, or so I think. But
Japan has contributed to my maturation in so many
ways other than scientific stature that I shall always
be beholding to Jim Neel and his invitation to be apart of this phenomenal study. Through this experience, I have learned to live with more of my senses,
and yet to respect the astringent, the under-stated.

Duncan McDonald (second from right) and William J. Schull(third from left) with the officers of the Hiroshima Midwives
Association in July 1951. This group collaborated in the
ABCC’s genetics program started in 1948.

RERF Update Volume 22, Issue 1, 2011

30

Human Interest Notes
Those of us who are native English speakers have at
our disposal a language incredibly responsive to
nuance, but despite this fact there is no counterpart
to the Japanese word “shibui” known to me. Having
said this it would be foolhardy to attempt a definition, but I can say that to me shibui implies a quiet

appropriateness of a thing, a place, I suppose even an
event, with regard to color, to shape, to size, to texture, and to touch. The remarks I made at RERF in
May of 2010 were an imperfect attempt to express
my regard for a land, a culture, and a people whohave taught me so much through quiet example.

Reaching Retirement Age
Kazuo Neriishi, Consultant
Department of Clinical Studies
Upon reaching
the time of mymandatory retirement at the end of
December 2010, I
would like to sharewith you some of
my memories of
RERF.
After completing
my medical internship at Nagasaki
University, I was
hired by Hiroshima RERF in 1979. As I stayed in
the United States for overseas study from 1981
through 1984, I actually worked at RERF for a totalof 28 years. For two-and-a-half years before visiting the United States, I studied English and radiation biology every day. I remember that I readthrough a thick volume of radiation biology as reference for seminars held by Dr. Kelly Clifton foryoung researchers. For three years from 1981
through 1984, I studied at Miami University in
Florida, with the aim of researching active oxygen,a subject attracting little attention in those days. Dr.
Lee Frank, my supervising professor, thoroughly
taught me the meaning of “scientific research.” I
was also greatly influenced by his sense of social
responsibility. I will never forget the thrill I had
upon finishing my first manuscript under his guidance.
After being assigned to the RERF Departmentof Clinical Studies in 1984, I decided to utilize myknowledge of active oxygen in epidemiologicalresearch. Although vitamins E and C as breast cancer inhibitors appeared to be promising topics, ourlyophilized (freeze-dried) serum samples were,
unfortunately, of no use. This experience gave
impetus to the holding of a symposium on serumsample preservation. Based on the recommendations expressed at the symposium, we decided on
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resumption of cryopreservation combined with useof lyophilization. Lyophilization, however, waslater abandoned completely. A breast-cancer study
was again conducted in 2002 and a series of related
publications are expected in the near future. Taking
over a study of benign monoclonal gammopathy(BMG) conducted by Dr. Motoko Mikami at the
Research Institute for Radiation Biology and Medicine, Hiroshima University, I embarked on this new
field of research (1985–1987). As Chief of theDivision of Clinical Laboratories, I launched in1986 a project of hematological and biochemical
testing for all Adult Health Study (AHS) participants. At the same time, I promoted a system forincluding test values in reports for the study participants. An association observed between inflammation and radiation exposure in relation to active
oxygen was an interesting finding.
My research focus in 1991 turned to epilation. I
found that the incidence of leukemia was threetimes higher in individuals who experienced epilation at the time of the bombings compared to those
not experiencing the disorder. Similar findings
were also observed for chromosome aberrations
and cataracts. My study theme was whether suchdifferences reflected variation in radiation sensitivity or dosimetry error. Recent reports have indicated that there are variations in radiation sensitivity as suggested by such molecular biomarkers as
ATM. A study of epilation using this marker would
be very interesting. Because ATM suppresses
development of active oxygen, it would be logicalto assume that inter-individual variation of thisaction could be associated with radiation sensitivity.
Following the 1986 Chernobyl nuclear accident,
the Hiroshima International Council for HealthCare of the Radiation-exposed (HICARE) wasestablished in 1991, resulting in my first-ever dispatch to Russia and extreme culture shock. Given
the responsibility for educational activities, I ultiRERF Update Volume 22, Issue 1, 2011

Human Interest Notes
mately realized this occasion would serve as animportant mission for RERF. I am pleased to learn
that RERF’s transition to a public-interest incorporated foundation has included a commitment toeducation and training activities. Ever since theJCO criticality accident in the Japanese town ofTokaimura in 1999, I have been involved in healthexaminations of the local residents. Due to a lackof accurate and sufficient information among both
the residents and local government staff, people
worry about long-term heath problems, occasionally leading to serious societal crises. In consideration of this point, I have worked on both physicaland mental health management for such individual
residents. I have learned through those activities
that I should not be so hasty to convince those who
are worried about health effects of radiation otherwise. Instead it is important to be someone withwhom they can discuss problems or questions at
any time. In that regard, I think my work was apositive contribution to the residents of Tokaimura.
My research focus shifted to ophthalmology
starting in 2000. Based on our research, it was
revealed that a dose-response relationship exists
not only with subcapsular cataracts, a relationshipthat had already been recognized for some time,
but also with cortical cataracts, and that the threshold dose for cataracts is lower than the level previously reported. I am very pleased and proud that
our research was able to provide an important basis
for, and contributed to, establishment of relevant
radiation safety standards at the International Commission on Radiological Protection (ICRP). We
also found a dose-response relationship as well as a
low-dose threshold for post-operation cataracts, amarker for severe cataracts. Those findings also
contributed to establishment of relevant radiation
safety standards. With the establishment in 2008 ofa system for collection and storage of surgicallyremoved tissues, I am looking forward to muchprogress in the future in molecular biologicalresearch using such tissue samples. I believe that
digitized ophthalmological images will greatly
contribute to future research. In addition, I anticipate that research on whether there is an association between glaucoma and radiation will makecontinued progress.
I am profoundly grateful to A-bomb survivors
and those scientists at university ophthalmology
departments and ophthalmologist associations fortheir cooperation, without which our study would
not have been possible. Furthermore, I realized
that, when faced with challenging situations, weshould not abandon our research, but instead,respond passionately to such situations in a sincere
and serious manner. For example, when I foundthat RERF’s visual field detector had not been

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31
designed to enable output of digitized data, I sent to
the president of the equipment’s manufacturer aletter explaining the importance of digitized data at
RERF. Arrangements were then made so that software allowing output of digitized data could be
developed exclusively for RERF. I was very grateful for the president’s efforts.
A radiation cataractogenesis workshop was heldat RERF in March 2009. Experts in the fields of
epidemiology, molecular biology, and ophthalmologic medicine from the Lawrence Berkeley
National Laboratory, Columbia University, Harvard
University, and NASA in the United States, as wellas Japanese counterparts from Kyoto University,
Hiroshima University, and Nagasaki University,
gathered at RERF and participated in substantive
discussions. Workshop participants discussed
expansion of a research protocol for storage ofcataract tissues and initiation of a new protocol
using the stored tissues, encouraging the advancement of comprehensive, collaborative research.
One unexpected finding from our research indicated that the difference in cataract prevalence
between Hiroshima and Nagasaki may be due tothe difference in quantity of ultraviolet-ray exposure. The latitudes of the two cities differ by only
1.6 degrees. Our research indicated, however, thatultraviolet rays might also be an important risk factor for potentially explaining the inter-city differences between Hiroshima and Nagasaki in terms ofskin cancer and other disorders (Minamoto A,
Neriishi K, Nakashima E. UV radiation may
explain intercity difference for cataract in A-bomb
survivors. J Photochem Photobiol B 2011; 103:105–
10). Amid the concerns over the biological impact
of depletion of the ozone layer, we may have contributed data relevant to that environmental issue
and how strong physical effects of radiation are. I
hope this research will progress further in the
future.
I would like to conclude my article by mentioning a letter from an AHS participant. The participant wrote in the letter: “I was recently diagnosed
as having acute myelogenous leukemia with a poor
prognosis. As I will be unable to visit RERF any
more to undergo health examinations, I would liketo enclose a copy of my examination results toserve as reference materials for your future
research.” A detailed medical history was also
enclosed. That person was apparently determined
to fully live what remained of life, calmly contemplating mortality. I continue to ask myself, “howcan I fully respond to the person’s wishes?” I
would like to close by expressing my sincere
appreciation to all of you for the kind support you
extended to me over so many years.

RERF Update Volume 22, Issue 1, 2011

Research Protocols

Research Protocols Approved in
November 2010–April 2011
RP 1-11 Study of Radiation-induced Circulatory Diseases Using Animal Models
Takahashi N, Niwa Y, Ohishi W, Hayashi T, Murakami
H, Hsu WL, Kokubo T, Inaba T, Kusunoki Y
The Life Span Study (LSS) data indicate radiation-associated risk for hypertensive heart disease
and stroke, and the Adult Health Study (AHS) datasuggest radiation-associated risk for hypertension.
We hypothesize that radiation may result in higher
risk for circulatory diseases (CD). However, there
are a limited number of animal model studies thathave examined the relationship between radiation
and CD at doses under 4 Gy, although some papers
report that various biomarkers are affected by radiation. In this study, we propose the use of spontaneous hypertension rat-stroke prone (SHRSP) rats
as rat CD models. Radiation doses from a brief
single exposure will be given to the rats at 4, 2, and1 Gy, with non-exposed (0 Gy) rats used as controls. We will evaluate acceleration of the development of hypertension in the SHRSP rats after radiation exposure. Moreover, we will measurecandidate serum markers that have shown radiationdose effects based on previous AHS studies. In
addition to serum markers, we will also measure 23
biomarkers in plasma samples by immunoassay.
The priority of each plasma marker will be determined on the basis of previous results from AHS
studies, and we plan to examine the effects of radiation exposure in morphological types in autopsy
tissues by collaborating with the Institute for Environmental Sciences. This study will provide mechanistic information on the association between
radiation exposure and development of CD.
RP 2-11 Study of Arteriosclerosis in the Adult
Health Study Population (Part 2. Analysis of
the Cytokine Network Regulating Differentiation of Mesenchymal Stem Cells in Artery)
Takahashi I, Ohishi W, Hayashi T, Cologne JB,
Takahashi T, Kusunoki Y, Ozasa K, Kihara Y,
Matsumoto M, Fujiwara S
Reports regarding therapeutic irradiation of thehuman head and animal experiments, as well asreports involving mortality and incidence of arteriosclerotic diseases among A-bomb survivors, havesuggested that high-dose radiation induces arteriosclerosis, but the mechanism of such induction is
unclear. It is difficult to explain the entire picture of
the complex clinical condition of arteriosclerosis
with the conventional hypothesis that arteriosclerosis is an inflammatory disease. Tissue damage isprobably of primary importance in relatively highdose-radiation-induced arteriosclerotic changes. In
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32
this study, therefore, we will consider arteriosclerosis based on the “inflammation-response-to-injury”
hypothesis. We hypothesize that diseases related to“artery-bone metabolism-immunity” are abnormalities in differentiation and proliferation of arterial
mesenchymal tissue. Thus, we also will measureseveral multi-functional cytokines in 2,100 Adult
Health Study (AHS) subjects (including those
exposed at young ages). That cross-sectional study
is designed to test our hypothesis that “abnormalities in the cytokine network initiated by tissue damage at the time of radiation exposure induce abnormalities in mesenchymal tissues.” We will obtainmeasurements of arteriosclerotic markers (augmentation index [AI]; brachial-ankle pulse wave velocity [baPWV]; ankle-brachial index [ABI]; intimamedia thickness [IMT]; calcification of aortic arch
and/or abdominal artery) and cytokines (pentraxin-3 [PTX-3]; osteopontin [OPN]; osteoprotegerin [OPG]; receptor activator of nuclear factor[NF]-κB ligand [RANKL]; vascular endothelial
growth factor-A [VEGF-A]; high mobility groupbox-1 [HMGB-1]; apolipoprotein-J [Apo-J], also
called clusterin; interleukin-17 [IL-17]), which will
be measured once during the four years (two cycles)
starting in 2010 that constitute our study period. We
also will measure reactive oxygen species (ROS),
which act as proliferation signals for mesenchymal
stem cells. We will then examine if the “cytokine
network” functions to either moderate or mediate
the radiation effect upon atherosclerotic cardiovascular outcomes.

RP 3-11 Radiation Exposure in Children andIn Utero Survivors of the Atomic Bombing ofHiroshima and Nagasaki and Late-life Neurocognitive Function
Yamada M, Hida A, Akahoshi M, Kasagi F, Abbott
RD, Khattree R, Ohshita T, Miyachi T, Matsumoto
M, Tsujino A, Mimori Y, Krull KR, Fujiwara S
We will examine late-life neurocognitive function among the Adult Health Study subjects who
were exposed in utero or aged <12 years at the timeof the atomic bombing of Hiroshima and Nagasaki.
Objectives are (1) to examine associations between
radiation exposure and neurocognitive function asassessed by neuropsychological examination, (2) toinvestigate the effects of sex, age, attained education, lifestyle, and comorbidity on neurocognitive
function as risk factors or modifiers of radiation
effects, and (3) to collect baseline data on cognitive
function for the investigation of longitudinal progression in cognitive decline with advancing age
and the occurrence of dementia. The Cognitive
Abilities Screening Instrument (CASI) and theChildhood Cancer Survivors Study (CCSS)-Neurocognitive Questionnaire (NCQ) will be used as
instruments for neuropsychological assessment.
RERF Update Volume 22, Issue 1, 2011

Recent Publications

Recent Publications(Japanese): the original article is in Japanese.

Adams MJ, Dozier A, Shore RE, Lipshultz SE,
Schwartz RG, Constine LS, Pearson TA, Stovall
M, Winters P, Fisher SG: Breast cancer risk 55+
years after irradiation for an enlarged thymus
and its implications for early childhood medical
irradiation today. Cancer Epidemiology,
Biomarkers and Prevention 2010 (January);
19(1):48-58.
Adams MJ, Shore RE, Dozier A, Lipshultz SE,
Schwartz RG, Constine LS, Pearson TA, Stovall
M, Thevenet-Morrison K, Fisher SG: Thyroid
cancer risk 40+ years after irradiation for anenlarged thymus: An update of the Hempelmanncohort. Radiation Research 2010 (December);174(6):753-62.
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K): Body-mass index and cancer mortality in the Asia-Pacific Cohort Studies Collaboration: pooled analyses of 424,519 participants.
Lancet Oncology 2010 (August); 11(8):741-52.
Bernstein JL, Haile RW, Stovall M, Boice JD Jr,
Shore RE, Langholz B, Thomas DC, Bernstein
L, Lynch CF, Olsen JH, Malone KE, Mellemkjaer
L, Borrensen-Dale A-L, Rosenstein BS, Teraoka
SN, Diep AT, Smith SA, Capanu M, Reiner AS,
Liang X, Gatti RA, Concannon P, the WECARE
Study Collaborative Group: Radiation exposure,
the ATM gene, and contralateral breast cancer inthe women’s environmental cancer and radiation
epidemiology study. Journal of the National Cancer Institute 2010 (April); 102(7):475-83.
Blakely EA, Kleiman NJ, Neriishi K, Chodick G,
Chylack LT, Cucinotta FA, Minamoto A,
Nakashima E, Kumagami T, Kitaoka T,
Kanamoto T, Kiuchi Y, Chang P, Fujii N, Shore
RE: Meeting report “Radiation cataractogenesis:
Epidemiology and biology.” Radiation Research2010 (May); 173(5):709-17.
Cologne JB: A few clarifications: Letter Re: Categorisation of continuous risk factors in epidemiological publications: a survey of current practice, by Turner EL, Dobson JE, Pocock SJ.
Epidemiologic Perspectives & Innovations 2010
(November); 7:9.
Cullings HM: A preliminary geospatial analysis of137
Cs measured in soil cores from Hiroshima.
Research group on the black-rain fallout of theHiroshima A-bomb, ed. Current status of studies
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33
on radioactive fallout with “black-rain” due tothe Hiroshima atomic bomb. Interim report ofresearch group on the black-rain fallout of theHiroshima A-bomb. 2010 (April), pp 119-33.
Cullings HM, Smith KR: Better radiation exposure
estimation for the Japanese atomic-bomb survivors enables us to better protect people fromradiation today. Journal of Exposure Science andEnvironmental Epidemiology 2010 (November);20(7):575-6. (Commentary and Review Series
1-10)
Douple EB: From out of the ruins. Disaster Medicine and Public Health Preparedness 2011
(March); 5(Suppl 1):S7.
Douple EB, Mabuchi K, Cullings HM, Preston DL,
Kodama K, Shimizu Y, Fujiwara S, Shore RE:
Long-term radiation-related health effects in aunique human population: Lessons learned fromthe atomic-bomb survivors of Hiroshima andNagasaki. Disaster Medicine and Public HealthPreparedness 2011 (March); 5(Suppl 1):S12233.
Grant EJ, Ozasa K: Ionizing radiation. Tuncer AM,
ed. Asian Pacific Organization for Cancer Prevention Cancer Report 2010. Ankara, Turkey:
New Hope in Health Foundation; 2010 (April),
pp 49-52.
Haraguchi A, Era A, Yasui J, Ando T, Ueki I, Horie
I, Imaizumi M, Usa T, Abe K, Origuchi T,
Eguchi K: Putative IgG4-related pituitary disease
with hypopituitarism and/or diabetes insipidus
accompanied with elevated serum levels of IgG4.
Endocrine Journal 2010 (September); 57(8):71925.
Hida A, Imaizumi M, Sera N, Akahoshi M, Soda
M, Maeda R, Nakashima E, Nakamura H, Ida H,
Kawakami A, Eguchi K: Association of human T
lymphotropic virus type I with Sjogren syndrome. Annals of the Rheumatic Diseases 2010
(November); 69(11):2056-7. (RERF Report
12-09)
Ishii R, Imaizumi M, Ide A, Sera N, Ueki I, Horie I,
Ando T, Usa T, Ejima E, Ashizawa K, Eguchi K:
A long-term follow-up of serum myeloperoxidase anti neutrophil cytoplasmic antibodies(MPO-ANCA) in patients with Graves disease
treated with propylthiouracil. Endocrine Journal
2010 (January); 57(1):73-9.
Iwanaga M, Hsu WL, Soda M, Takasaki Y, Tawara
M, Joh T, Amenomori T, Yamamura M, Yoshida
RERF Update Volume 22, Issue 1, 2011

Recent Publications
Y, Koba T, Miyazaki Y, Matsuo T, Preston DL,
Suyama A, Kodama K, Tomonaga M: Risk of
myelodysplastic syndromes in people exposed toionizing radiation: A retrospective cohort studyof Nagasaki atomic bomb survivors. Journal of
Clinical Oncology 2011 (February); 29(4):42834. (RERF Report 14-09)
Kusunoki Y, Hamasaki K, Koyama K, Imai K,
Hayashi T, Martin PJ, Nakachi K: Increased
DNA damage in hematopoietic cells of micewith graft-versus-host disease. Mutation
Research-Fundamental and Molecular Mechanisms of Mutagenesis 2010 (July); 689(1-2):5964. (RERF Report 13-08)
Kusunoki Y, Yamaoka M, Kubo Y, Hayashi T,
Kasagi F, Douple EB, Nakachi K: T-cell immunosenescence and inflammatory response inatomic bomb survivors. Radiation Research2010 (December); 174(6):870-6. (RERF Report
3-09)
Kusunoki Y, Yamaoka M, Kubo Y, Hayashi T,
Kasagi F, Nakachi K: Effects of atomic-bombradiation on human immune response. Report
25: A dose-dependent increase in the percentageof regulatory CD4 T cells. Nagasaki Igakkai
Zasshi [Nagasaki Medical Journal] 2010 (September); 85(Special Issue):282-6. (Proceedingsof the 51st Late A-bomb Effects Research Meeting, 2010) (Japanese)
Langholz B, Thomas DC, Stovall M, Smith SA,
Boice J Jr, Shore RE, Bernstein L, Lynch CF,
Zhang X, Bernstein JL: Statistical methods foranalysis of radiation effects with tumor and dose
location-specific information with application to
the WECARE study of asynchronous contralateral breast cancer. Biometrics 2009 (June);
65(2):599-608.
Lin Y, Nakachi K, Ito Y, Kikuchi S, Tamakoshi A,
Yagyu K, Watanabe Y, Inaba Y, Tajima K, for the
JACC Study Group: Variations in serum transforming growth factor-beta1 levels with gender,
age and lifestyle factors of healthy Japanese
adults. Disease Markers 2009 (November);27(1):23-8.
Mabuchi K, Fujiwara S, Preston DL, Shimizu Y,
Nakamura N, Shore RE: Atomic-bomb survivors: Long-term health effects of radiation.
Shrieve DC, Loeffler JS, eds. Human Radiation
Injury. Philadelphia: Lippincott Williams &Wilkins; 2010 (October), pp 89-113. (Commentary and Review Series 3-09)

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34
Minamoto A, Neriishi K, Nakashima E: UV radiation may explain intercity difference for cataract
in A-bomb survivors. Journal of Photochemistry
and Photobiology B: Biology 2011 (May);
103(2):105-10. (RERF Report 5-10)
NAS-NRC Committee (RERF: Shore RE) (Edit):
Review of the Toxicologic and Radiologic Risks
to Military Personnel from Exposures to
Depleted Uranium During and After Combat.
Washington DC: National Academies Press;
2008, 154 p.
Neriishi K: A hypothesis: Effects of malnutrition
exposure in prenatally or natally exposed A-bomb
survivors. Igaku no Ayumi [Journal of Clinicaland Experimental Medicine] 2010 (November);
235(8):863-6. (Japanese)
Noda A, Hirai Y, Kodama Y, Kretzschmar WW,
Hamasaki K, Kusunoki Y, Mitani H, Cullings
HM, Nakamura N: Easy detection of GFP-positive mutants following forward mutations at specific gene locus in cultured human cells. Mutat i o n R e s e a r c h - G e n e t i c To x i c o l o g y a n dEnvironmental Mutagenesis 2011 (March);
721(1):101-7. (RERF Report 11-10)
Ozasa K, Shimizu Y, Sakata R, Sugiyama H, Grant
EJ, Soda M, Kasagi F, Suyama A: Risk of cancer
and non-cancer diseases in the atomic bomb survivors. Radiation Protection Dosimetry 2011
(April); 1-4. (Epub ahead of print)
Pham TM, Fujino Y, Nakachi K, Suzuki K, Ito Y,
Watanabe Y, Inaba Y, Tajima K, Tamakoshi A,
Yoshimura T: Relationship between serum levels
of insulin-like growth factors and subsequentrisk of cancer mortality: Findings from a nested
case-control study within the Japan collaborative
cohort study. Cancer Epidemiology 2010 (June);
34(3):279-84.
Samartzis D, Nishi N, Hayashi M, Cologne JB,
Cullings HM, Kodama K, Miles EF, Funamoto
S, Suyama A, Soda M, Kasagi F: Exposure toionizing radiation and development of bone sarcoma: New insights based on atomic-bomb survivors of Hiroshima and Nagasaki. Journal of
Bone and Joint Surgery-American Volume 2011
(April); 93:1-8. (Epub ahead of print) (RERF
Report 9-08)
Shore RE: Implications of radiation epidemiologic
data for risk assessment and radiation protection.
Health Physics 2011 (March); 100(3):306-8.
(Abstracts of the Biological Consequences and
Health Risks of Low-level Exposure to Ionizing
RERF Update Volume 22, Issue 1, 2011

35

Recent Publications
Radiation, Richland, Washington, USA, 3–5
May 2010)
Shore RE, Neriishi K, Nakashima E: Epidemiological studies of cataract risk at low to moderateradiation doses: (Not) seeing is believing. Radiation Research 2010 (December); 174(6):889-94.
(RERF Report 9-10)
Stovall M, Smith SA, Langholz BM, Boice JD,
Shore RE, Andersson M, Buchholz TA, Capanu
M, Bernstein L, Lynch CF, Malone KE, AntonCulver H, Haile RW, Rosenstein BS, Reiner AS,
Thomas DC, Bernstein JL: Dose to the contralateral breast from radiotherapy and risk of second
primary breast cancer in the WECARE study.
International Journal of Radiation Oncology,
Biology, Physics 2008 (November); 72(4):102130.
Suyama A: Children of atomic-bomb survivors.
Nagasaki Association for Hibakusha’s Medicalcare (NASHIM), ed. Hibakusha in the 21st Century—Hibakusha in the World and Forefront of
Study on Radiation Diseases. Nagasaki: Nagasaki
Press; 2011 (March), pp 54-61. (Japanese)
Suyama A: A-bomb radiation effects on humanbody. Nagasaki Association for Hibakusha’s
Medical care (NASHIM), ed. Hibakusha in the
21st Century—Hibakusha in the World and Forefront of Study on Radiation Diseases. Nagasaki:
Nagasaki Press; 2011 (March), pp 118-28. (Japanese)
Takahashi N, Satoh Y, Sasaki K, Shimoichi Y,
Sugita K, Katayama H: Characteristics of highly
polymorphic segmental copy-number variations
observed in Japanese by BAC-array-CGH. Journal of Biomedicine and Biotechnology 2011
(January); 1-11 (Article ID 820472)
Tamakoshi A, Suzuki K, Lin Y, Ito Y, Yagyu K,
Kikuchi S, Watanabe Y, Inaba Y, Tajima K,
Nakachi K, for JACC Study Group: Relationshipof sFas with metabolic risk factors and their clusters. European Journal of Clinical Investigation2010 (June); 40(6):527-33.

38(8):1-9.
Xue X, Kim MY, Shore RE: Cox regression analysis in presence of collinearity: An application toassessment of health risks associated with occupational radiation exposure. Lifetime Data Analysis 2007 (July); 13(3):333-50.
Xue X, Kim MY, Shore RE: Estimation of healthrisks associated with occupational radiation
exposure: Addressing measurement error andminimum detectable exposure level. Health
Physics 2006 (December); 91(6):582-91.

Publications Using RERF Data
The following publications represent research done by
non-RERF scientists based on the data publicly available from RERF.

Jacob P, Walsh L, Eidemuller M: Modeling of cell
inactivation and carcinogenesis in the atomic
bomb survivors with applications to the mortality
from all solid, stomach and liver cancer. Radiation and Environmental Biophysics 2008 (July);
47(3):375-88.
Schneider U, Walsh L: Cancer risk estimates fromthe combined Japanese A-bomb and Hodgkincohorts for doses relevant to radiotherapy. Radiation and Environmental Biophysics 2008 (April);47(2):253-63.
Walsh L: A short review of model selection techniques for radiation epidemiology. Radiation andEnvironmental Biophysics 2007 (August);
46(3):205-13.
Walsh L: Heterogeneity of variation of relative risk
by age at exposure in the Japanese atomic bomb
survivors. Radiation and Environmental Biophysics 2009 (August); 48(3):345-7.
Walsh L, Jacob P, Kaiser JC: Radiation risk modeling of thyroid cancer with special emphasis on
the Chernobyl epidemiological data. Radiation
Research 2009 (October); 172(4):509-18.

Utada M, Ohno Y, Hori M, Soda M, Suyama A:
Analysis of the standardization and centralization for cancer treatment in Nagasaki Prefecture.
Asian Pacific Journal of Cancer Prevention 2010;11(2):409-12.
Walchuk M, Roessler G (interviewees: Douple EB,
Cullings HM): 65 years of radiation effects
research. Health Physics News 2010 (August);
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RERF Update Volume 22, Issue 1, 2011