Consultancy Meeting on Science, Technology and Society Perspectives
on Nuclear Science, Radiation and Human Health:The International Perspective
23 May 2017
Hiroshima, Japan

Long-term Epidemiological Studies onRadiation Effects in A-bomb Survivors
Kazunori Kodama, MD, PhD, FACC, FFPH
Chief Scientist
Director, Biosample Center
Chief, Nuclear Workers Health Study Office
Radiation Effects Research Foundation1

Outline of Presentation
1. Epidemiological studies on healtheffects of atomic bomb radiation
2. Study results1) Atomic bomb survivors
・Cancers・Diseases other than cancers
2) F1 offspring
3. Future perspectivesStudies on Health Effects of A-bomb Radiation- History 1945

’47 ’48

〃1975

2000

Atomic Bomb Casualty
Commission (ABCC)

Hiroshima
6 AugustNagasaki
9 August

Japanese National
Institute of Health

28 years

Radiation Effects
Research Foundation(RERF)
42 yearsLong-term Epidemiological Studies ofAtomic Bomb Survivors and Their Offspring
Atomic National Unified Study Launch ofProgram
Bomb Census
Program1945 1947 1950

1955

〃1958 1960

1970 1980

A-bomb survivors (120,000)

Mortality

1990 2000 2010

Life Span Study (LSS)

Cancer incidence

Adult Health Study (AHS)

Morbidity (24,000)

In-utero exposed (3,600)

Mortality
Cancer incidence
Morbidity (1,000)

Offspring (F1) (77,000)

Mortality
Cancer incidence
Morbidity (12,000)

Long-term Epidemiological Studies ofAtomic Bomb Survivors• The cohort study of the Japanese survivors of theatomic-bombings of Hiroshima and Nagasaki isbroadly considered one of the most reliable
sources of information on radiation health effects
because of the size and nature of the population
investigated and the scale of the data available.
• For this reason, the study has become
fundamental to the risk assessment of radiation
exposure and study results have been utilized by
the international organizations, such as
UNSCEAR, ICRP, IAEA and other authorities.
9Outline of Presentation
1. Epidemiological studies on healtheffects of atomic bomb radiation
2. Study results1) Atomic bomb survivors
・Cancers
・Diseases other than cancers
2) F1 offspring
3. Future perspectives

Outline of Presentation
1. Epidemiological studies on healtheffects of atomic bomb radiation
2. Study results1) Atomic bomb survivors
・Cancers
・Diseases other than cancers
2) F1 offspring
3. Future perspectives

(Grant EJ et al: Radiat Res 2017; 187: DOI: 10.1667/RR14492.1)

Radiation Risks of All Solid Cancers
ERR per Gy
Sex-averagedMalesFemales(95% CI)(95% CI)(95% CI)
Unadjusted for smoking
0.50
0.36
0.65
(0.42 to 0.59)(0.28 to 0.45)(0.53 to 0.77)
Adjusted for smoking, additive joint effect
0.56
0.48
0.64
(0.46 to 0.66)(0.36 to 0.61)(0.52 to 0.76)
Adjusted for smoking, multiplicative joint effect
0.47
0.33
0.60
(0.39 to 0.55)(0.25 to 0.42)(0.49 to 0.72)(Grant EJ et al: Radiat Res 2017; 187: DOI: 10.1667/RR14492.1)

Solid Cancer Incidence- Dose Response -Sex-averaged at age 70 for exposure at age 30(Grant EJ et al: Radiat Res 2017; 187: DOI: 10.1667/RR14492.1)

Lowest Significant Dose Range(LSS, Cancer Incidence, 1958-2009)
The lowest dose range for which there
are statistically significant risks:• 0-100 mGy• Sex-averaged linear ERR model• No adjustment for smoking• ERR = 0.49/Gy (95%CI:0.026-1.01)(Grant EJ et al: Radiat Res 2017; 187: DOI: 10.1667/RR14492.1)

Site-specific Cancer Risk (LSS, Incidence, 1958-1998)
All solidBladder
Other solid
BreastLung
Brain/CNS
Ovary
Thyroid
Colon
Esophagus
Oral cavity
StomachLiver
Pancreas
RectumN-M skin
Renal cell
Prostate
UterusGallbladder

-0.5

0.0

0.5

ERR

1.0

1.5

2.0

gender-averaged for 1 Gy at age 70 after exposure at age 30(Preston DL et al. RERF UPDATE 2007; 18: 9-13)

Cancer and leukemia
Other findings:• Cancer risk elevation associated with A-bombradiation exposure seems to continue for thelifetime.
• Leukemia risk elevation also persists.
• Myelodysplastic Syndrome (MDS) risk appears tobe increased.
• The increases in the risk of first primary andsecond primary cancers seem comparable.
• Radiation effects on lung cancer risk seem to bestronger among smokers.

Outline of Presentation
1. Epidemiological studies on healtheffects of atomic bomb radiation
2. Study results1) Atomic bomb survivors
・Cancers
・Diseases other than cancers
2) F1 offspring
3. Future perspectives

(Takahashi I et al. Radiat Res 2017;187: 319-332)

Heart Disease Subtype-Specific Risk
(LSS, Mortality, 1950-2008)(Takahashi I et al. Radiat Res 2017;187: 319-332)

ERR/Gy

Heart Disease Subtype-Specific Dose Response(LSS, Mortality, 1950-2008)(Takahashi I et al. Radiat Res 2017;187: 319-332)

A-bomb Radiation and CVD- Summary of RERF Findings • Mortality study indicated an elevated risk of heartdisease at doses above 0.5 Gy.
• Among heart diseases, hypertensive heart disease
and rheumatic heart disease are showing elevatedrisk in mortality.
• There are additional findings indicating elevatedrisk of stroke mortality, myocardial infarction
incidence, CKD mortality, and elevation of risk
factor levels, presence of inflammation, andalteration of immune function associated withradiation dose.
Kodama 18

A-bomb Radiation and CVD- Summary of RERF Findings • Dose-response relationship appeared to be linear
for HD mortality. However, there are indications
that dose-response could be linear-quadratic orquadratic for other CVD endpoints, such as strokemortality, incidence of myocardial infarction,incidence of hypertension and mortality of renal
failure.
• However, it is still unclear that the observed
association has causal link or not.
• It is also unclear whether the biologicalmechanisms operating at high doses of radiation
apply to lower doses.
Kodama 19(Wondergem J et al. Radiat Environ Biophys 2013;52:425-434)

Cardiovascular effects after low-dose exposureand radiotherapy: what research is needed?
- Recommendation for Epidemiological Studies1. Subtype specific risk estimations• Epidemiological studies, evaluating all heartdiseases together, are not expected to solve theimportant questions.
• Each disease may have a different pathogenesis,
a different clinical manifestation and a different
prognosis.
• Once specific radiation-induced heart diseases
are identified and risk estimation has been made,measures for primary and secondary prevention
can be implemented.
K. Kodama,(Wondergem J et al.
RadiatCRH2016
Environ Biophys 2013;52:425-434)30

Cardiovascular effects after low-dose exposureand radiotherapy: what research is needed?
- Recommendation for Epidemiological Studies2. Dose response analysis• With regard to the risk estimation in prospectivecohort studies, attention should be placed on
dose-response analysis based on individual
dose to identify whether dose responses arelinear or nonlinear.
• In the A-bomb survivor’s data, the dose
response of some specific heart diseases may
well be nonlinear such as the linear-quadratic orquadratic dose dependence of the incidence of
myocardial infarction.
K. Kodama,(Wondergem J et al.
RadiatCRH2016
Environ Biophys 2013;52:425-434)30

Outline of Presentation
1. Epidemiological studies on healtheffects of atomic bomb radiation
2. Study results1) Atomic bomb survivors
・Cancers
・Diseases other than cancers
2) F1 offspring
3. Future perspectives

Health Effects among F1 Offspring ofA-bomb Survivors• Past studies (e.g., studies of birth defects,sex ratio, and chromosome aberrations, andbiochemical studies) reported no geneticeffects.
• Ongoing studies (mortality, cancer incidence,and health examination studies) have yet toshow evidence that parental radiation
exposure increases disease risks among F1offspring.

Outline of Presentation
1. Epidemiological studies on healtheffects of atomic bomb radiation
2. Study results1) Atomic bomb survivors
・Cancers
・Diseases other than cancers
2) F1 offspring
3. Future perspectives

Future Perspectives• Radiation-associated cancer and noncancer diseases
will likely increase in the next 10-15 years.
• Accumulated epidemiological data will continue tolead to important findings on radiation-associatedcancer and noncancer disease risks.
• Continued epidemiological studies are essential forrisk assessment among A-bomb survivors exposed
at age 20 or under.
• For elucidation of mechanisms of radiationassociated diseases, research based on storedbiosamples and animal experiment will become
increasingly important.

Peace Memorial Park, HiroshimaThank you for listening!