RERF Study Cohorts

Life Span Study (LSS)In Utero
StudyChildren of Atomic-bomb
Survivors (F1) Study

120,000

3,600

77,000Adult Health Study (AHS)
25,000（1,000）

Clinical Study of the F1
Offspring of A-bomb
Survivors 12,000■Life Span Study
The Life Span Study is an epidemiological research program investigating lifetime health effects of atomicbomb radiation. Its major objective is to investigate long-term effects from A-bomb radiation on causes of deathand incidence of cancer. About 120,000 subjects selected from among residents of Hiroshima and Nagasakiidentified through the 1950 national census have been followed since that time, including about 94,000 A-bomb
survivors and about 27,000 unexposed individuals.

■Adult Health Study
The Adult Health Study is a clinical study of a sub-cohort of the Life Span Study. Examinations of the A-bomb
survivor subjects of the study are conducted every two years, providing a continuous health profile of this aging
population. In addition, blood samples for future analysis are collected on the basis of the examinees’ informedconsent. This study strives to establish radiation-related risk of noncancer diseases and investigate aging- andradiation-related physiological changes. It will be continued throughout the lifetimes of the survivors to moreaccurately grasp radiation’s association and risk in noncancer disease development. The study also provides
useful information for the health management of A-bomb survivors.

■In Utero Study
The In Utero Study is designed to examine lifetime health status of about 3,600 persons who were in the wombat the time of bombing. It is known that, depending on radiation dose, persons exposed at 8–15 weeks ofgestation have shown an elevated risk of microcephaly and intellectual impairment. To date, cancer incidence inindividuals exposed prenatally tends to increase with radiation exposure dose at around the same level as
incidence in those exposed in childhood (the period 0–5 years). It is considered that many findings will beobtained by continued follow-up of this in utero study cohort.

■Children of Atomic-bomb Survivors (F1) Study
The Children of Atomic-bomb Survivors Study conducts research on such children to determine whether any
genetic effects exist that could be related to parental exposure. An initial study of birth defects did not reveal any
discernable effects. Subsequent studies on mortality and cancer incidence, chromosome abnormalities, andserum proteins were also conducted, but again no parental exposure effect was observed. Presently, thesemortality and cancer-incidence follow-up studies are being continued, with DNA studies recently initiated.
Starting in 2002, a new clinical study was initiated to investigate lifestyle-related diseases that are not observableat birth but only start to appear in middle age (e.g., hypertension, diabetes mellitus, etc.). This clinical study isstill being conducted today.

Study details

Number of study subjects

Study period① Physical abnormalities at birth

77,000 persons

1948–1954② Chromosome aberrations

16,000 persons

1967–1985③ Abnormalities in blood protein

24,000 persons

1975–1985④ Mortality and cancer incidence

77,000 persons

1946–present⑤ Clinical examination of lifestyle diseases

12,000 persons

2002–present

Radiation Effects Research Foundation

Late Effects from Radiation■Cancer Incidence and Mortality among
A-bomb Survivors

Numbers of people dying of leukemia and thosecontracting cancer in the Life Span Study cohort
Leukemia(Deaths)(1950–2000)

93/204(46%)

Cancers(Incidence)(1958–1998)

850/7,851
(11%)
02000

4000

6000

Extent of increase in excess leukemia andcancer mortality due to radiation exposure(schematic diagram)
Number of deaths
per year

It has been found that cancer incidence and mortality arehigher among A-bomb survivors than among theunexposed (see the figure at right). The largest percentage
increase in cancer incidence and mortality due to radiation
exposure is shown for leukemia. Leukemia started toincrease two or three years after exposure, reached a peakafter five to ten years, and decreased thereafter. However,incidence and mortality from leukemia still appear even
now to be slightly higher in A-bomb survivors than in theunexposed. On the other hand, solid cancers (all cancers
other than leukemia) started to increase about ten years
after exposure and have continued to rise with time.

Solid cancers
Leukemia

0102030

5040

Years since radiation exposure

The numbers of leukemia deaths and cancer cases amongA-bomb survivors exposed to at least 0.005 Sv (5 mSv) inthe Life Span Study cohort are shown in the figure at left.
The blue portions (about half of leukemia deaths and about
10% of cancer cases) indicate excess leukemia deaths andcancer cases attributable to radiation exposure.

8000 (cases)■Radiation Risk (at age of 70)

Cancer risk from radiation exposure
2Radiation risk (times)

RERF’s epidemiological research of A-bomb survivors hasrevealed that exposure to radiation dose of 1 Sv (1,000 mSv) atage 30 increases mortality risk from solid cancers at age 70 an
average of about 1.5 times for both sexes. The risk increases in
direct proportion to radiation dose above around 100 to 200mSv. However, association remains unclear below that range. If
we assume that cancer risk is proportional to radiation without“threshold” (the demarcation point above which there are effects
and below which there are no effects), projections indicate that
exposure to 100 mSv and 10 mSv increases cancer risk by
about 1.05 and 1.005 times, respectively.

01.5
1.25
1.05

1005001001000

2000

Radiation dose (millisievert)■Radiation Risk (lifetime)
Based on the above data, exposure to radiation dose of about 100 mSv at age 30 is thought to increase thelifetime risk of cancer mortality from 20% without radiation exposure to about 21% (1 percentage point increase)on average for both sexes. A-bomb exposure was a single acute exposure, while environmental contamination
represents chronic exposure. The effects from chronic exposure, even in the case of the same total dose, arethought to be smaller than the effects from acute exposure (1/2 or 1/1.5). Based on this theory, chronic
exposure to about 100 mSv would increase lifetime risk by 0.5 to 0.7 of a percentage point. Based on thestudies of A-bomb survivors, it is also known that risk from radiation is larger for those exposed when young as
shown in the table below.
Cancer risk after single 100 mSv exposure

Age at time of exposure
10 years of age
30 years of age
50 years of age

Lifetime excess
risk (%)

Lifetime risk without
exposure (%)

Males

2.1%

30%

Females

2.2%

20%

Males

0.9%

25%

Females

1.1%

19%

Males0.3%

20%

Females

0.4%

16%

Sex

Radiation Effects Research Foundation

Estimation of Radiation Dose
■Physical Dosimetry
10100.5
0.5

Radiationdose (sievert)
放射線の量（グレイ）Radiation
放射線の量（グレイ）dose (sievert)

With the introduction of an A-bomb radiation
dosimetry system, it became possible toestimate individual doses based on information
concerning each survivor’s location andshielding status at the time of bombing. The
current dosimetry system was introduced in
2002 and is therefore called DS02. DS02 wascreated employing the latest data from nuclear
physics. DS02 estimates are consistent withmeasurements obtained from exposedmaterials collected after the bombings,
including bricks and tiles.

88
6420.4
0.4
0.3
0.3
0.2
0.2
0.1
0.1
0.0
0.000
1.0
1.0

1.5
1.5

2.0
2.0

2.5
2.5

爆心地からの距離（km）
Distancefrom hypocenter (km)

1.5
1.5

2.0
2.0

2.5
2.5

Distance爆心地からの距離（km）
from hypocenter (km)This figure shows relationship between distance from thehypocenter and air dose (without shielding), according to DS02.
When a person is exposed to radiation in a typical Japanesehouse, radiation decreases to half of the doses presented here.

■Biological Dosimetry
In addition to the radiation dosimetry system DS02, we use
a method utilized since the 1960s for studying
chromosomes. One cc of blood contains a few million
lymphocytes (one kind of white blood cell). When cells start
dividing after being cultured for two days, chromosomes canbe observed. Microscopic examination of abnormalities
called translocations that occur in the chromosomes will
reveal roughly how much radiation someone was exposedto (see the image at right). It is also possible to estimate
radiation dose by using a technique called electron spinresonance (ESR) on the enamel of an extracted tooth.

The image shows adividing cell withabnormalities, asindicated by the arrows.
Abnormalchromosomes(translocations) shownin two colors were
produced by exchange
between segments of
two different
chromosomes.

Mechanistic Studies of Radiation’s Effects on the Body
■Immunological Study
Alterations in the immune system associated with aging
and A-bomb radiation dose have been observed in A-bomb
survivors. By analyzing the numbers and functionalchanges of various types of immune cells, we study
whether aging of the immune system, a process thatappears to be accelerated by radiation, may be related tothe increased risk of several aging-associated diseases
among A-bomb survivors including cardiovascular disease
and selected cancers (see the figure at right).

Late effectsof radiation

Natural aging
Alterations in number andfunction of immune cells

Radiation

ThymusT cells

Inflammatory
cytokines
Persistent
inflammation

NK cells■Genome Study
B cells?
Inflammation‐ andaging‐associated
It is said that tendency to develop radiation-related diseases
diseases,varies with each person. One of the reasons for this difference ise.g., cancer,
Stem cells
cardiovascularbelieved to be slight variations in the structure of genes among
Mutationsdiseasesindividuals. Association between risks of development of various
diseases and the entire gene structure (the genome) is being
studied worldwide, with the aim of using such knowledge for prevention of diseases as well as development ofrelated drugs. At RERF, we use some of the blood samples from our clinical study participants for genome
studies, with their consent, for understanding the mechanisms that explain how radiation causes diseases for thepurpose of preventing future radiation-related diseases and developing treatments for such diseases.

■Radiation-related Carcinogenesis Study
We study at the molecular level characteristics of cancers developing from radiation exposure. Normal cells
develop into cancer cells as a result of an accumulation of various gene abnormalities. Many cancers haveseveral patterns in terms of types of related genes and their abnormalities. Our studies of thyroid and coloncancers suggest that particular patterns (accumulation of characteristic abnormalities in specific genes) arefrequently observed in radiation-related cancers.
Radiation Effects Research Foundation