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Cynthia H. McCollough, PhD: Radiation as a
carcinogen
May 13, 2008- 10:15 AM
CARCINOGENS
Radiation As A Carcinogen
Cynthia H. McCollough, PhD
Director, CT Clinical Innovation Center
Department of Radiology
Mayo Clinic
Rochester, MN
Type
Example
Physical
Ionizing radiation
Chemical
Cigarette Smoke
Biological
Viruses (e.g. Human
papilloma virus (HPV)
causes ~70% of cervical
cancers
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2008
X-rays are ionizing radiations
Radiation Damage to
Chromosomes
• Indirect damage
– Water molecule is ionized, breaks
apart, and forms OH free radical.
– OH free radical contains an
unpaired electron in the outer
shell and is highly reactive:
Reacts with DNA.
– 75 percent of radiation-caused
DNA damage is due to OH free
radical.
• Direct damage
– DNA molecule is struck by
radiation, ionized, resulting in
damage.
What Follows Chromosome
Damage?
• The cell might:
– Repair mild damage.
– Have mild damage that sits inactive until
another agent interacts with the same cell.
– If it is a reproductive cell like sperm or egg
cells, have damage to the genetic code that
doesn’t show up until future generations
– Have some damage causing it to become a
cancer.
– Stop functioning.
– Be killed.
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Cell Sensitivity
• Actively dividing cells are most sensitive to
radiation damage.
– Tissues that are more sensitive include skin,
hair, replacement of blood cells, and lining of the
intestine.
– Tissues that are less sensitive include muscle,
bone, brain, and connective tissue.
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Cynthia H. McCollough, PhD: Radiation as a
carcinogen
Cancer
• Radiation-induced cancers do not appear until at
least 10 years after exposure (for tumors) or 2 years
after exposure (for leukemia).
• The time after exposure until possible cancer
formation is called the “latent period.”
• The risk of cancer after exposure can extend
beyond this latent period for the rest of a person’s
life for tumors or about 30 years for leukemia.
May 13, 2008- 10:15 AM
IONIZING RADIATION AS A
CARCINOGEN
• Production of tumors noted in early radiation
workers
• Radiation carcinogenesis in small animals is
well documented
• Several sources of information on
carcinogenesis in humans:
– Atomic bomb survivors
– Medical populations
Risk Uncertainties
Linear No-Threshold Hypothesis
• Early 1950s, scientific groups creating
radiation protection guidelines:
– Effects of radiation at low doses not known
– Decided to assume that the radiation dose and the
effect of the dose were linear and proportional.
– Decided that any dose, no matter how small,
could cause an effect (no threshold).
• Setting radiation protection standards
required “erring” on the “safe” side—setting a
standard lower than it may have to be if the
real level of hazard were known. This is the
basis for LNT.
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Cynthia H. McCollough, PhD: Radiation as a
carcinogen
HUMAN DATA
•
•
•
•
Leukemia and cancer in atomic bomb survivors.
Lung cancer in uranium miners.
Bone cancer in radium dial painters.
Leukemia in patients treated for ankylosing
spondylitis.
• Thyroid cancer in children treated for enlarged
thymus.
• Breast cancer in women treated for tuberculosis.
• Thyroid cancer in Marshallese exposed to fallout.
May 13, 2008- 10:15 AM
EXAMPLES OF EXPOSURE
FROM NUCLEAR WEAPONS
OR FALLOUT
Study Group:
Radium dial painters: 1500 women
in U.S. watch dial industry.
Radiation:
alpha particles, up to 500 Gy to bone
Date of Exposure:
1915 - 1930
Reason:
Occupational exposure: smoothed
tips of brushes with tongue to paint
radium on watch dials.
Results:
Bone cancer
Therapy for ankylosing spondylitis:
13,000 patients in Great Britain.
Radiation:
X-rays: up to 30 Gy to spine
Date of Exposure:
1935 - 1954
Reason:
Radiotherapy for immobility of
backbone.
Results:
Increased incidence of leukemia and
other cancers in exposed population.
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up to 4 Gy
Date of Exposure:
August 1945
Reason:
Wartime attack
Results:
Leukemia, lymphoma, thyroid
cancer, breast cancer
EXAMPLES OF MEDICAL
EXPOSURES
Study Group:
Enlarged thymus: 2,400 patients
exposed in infancy.
Radiation:
X-rays: dose unknown
Date of Exposure:
Prior to 1959
Reason:
Therapy for thymic enlargement.
Results:
Thyroid cancer
EXAMPLES OF MEDICAL
EXPOSURES
Study Group:
γ, neutrons:
Radiation:
EXAMPLES OF
OCCUPATIONAL EXPOSURES
Study Group:
Japanese atom bomb survivors:
108,000 in Hiroshima and Nagasaki
EXAMPLES OF MEDICAL
EXPOSURES
Study Group:
Fluoroscopy of TB patients: 1,800
women in Massachusetts.
Radiation:
X-rays: up to 6 Gy to breast
Date of Exposure:
1930 - 1954
Reason:
Therapy for TB
Results:
Breast cancer
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Cynthia H. McCollough, PhD: Radiation as a
carcinogen
FACTORS INFLUENCING
RADIATION - INDUCED CANCER
• Radiation dose & dose rate
• Radiation quality (LET)
• Sex
• Age
May 13, 2008- 10:15 AM
THYROID CANCER
Thyroid has high sensitivity to radiation-induced
carcinogenesis.
Sources of Information:
• Hiroshima and Nagasaki
• Children exposed for enlarged thymus, tinea capitis
• Marshall Islanders
• Chernobyl (children)
THYROID CANCER
• Higher in women than men
(by a factor of 2)
• Children at higher risk
• Latent period - 25 years or more
BREAST CANCER
Female breast has high sensitivity to radiation induced
carcinogenesis (similar to thyroid)
Sources of Information:
• Women given multiple fluoroscopic examinations during
artificial pneumothorax for pulmonary TB
• Women treated by X-ray for postpartum mastitis
• A-bomb survivors
BREAST CANCER
BONE CANCER
• Women exposed before age 30 appear to have
higher risk
Sources of Information:
• Latent period: 25 years
• Ankylosing spondylitis patients treated with xrays
• Fractionation of radiation dose does not
significantly affect risk
• Radium dial painters
• Radium therapy of bone tuberculosis or
ankylosing spondylitis
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Cynthia H. McCollough, PhD: Radiation as a
carcinogen
May 13, 2008- 10:15 AM
BONE CANCER
RISK OF CANCER
• High LET radiation (alpha particles from radium)
more effective than xx-rays
• Not known very well at low doses
• Most available data at high doses
• Younger individuals have higher risk (20 years or
younger)
• Different cancers may have different doseresponse curves
• Threshold dose - approx. 5 Gy
• Risk estimates depend on shape of doseresponse curves
CANCER INCIDENCE IN SURVIVORS OF
THE ATOMIC BOMBINGS
CANCER INCIDENCE IN SURVIVORS OF
THE ATOMIC BOMBINGS
Leukemia, 1950 - 1987
Solid Tumor Incidence, 1958 - 1987
Absorbed dose
(Gy)
<0.01
0.01 - 0.1
0.1 - 0.2
0.2 - 0.5
0.5 - 1
1-2
>2
Total
Observed
4,286
2,223
599
759
418
273
55
Expected
4,281
2,174
553
637
290
146
20
8,613
8,103
CANCER RISK
Source
Deaths/Million persons/10 mGy
BEIR 1972
BEIR 1980
UNSCEAR 1977
BEIR 1990
BEIR VII 2006
males
females
117
77
100
400
410
610
Absorbed dose
(Gy)
<0.01
0.01 - 0.1
0.1 - 0.2
0.2 - 0.5
0.5 - 1
1 - 1.5
1.5 - 2
2-4
Observed
90
38
8
27
24
19
8
17
Expected
81
42
11
12
6
2
1
1
231
156
Total
CANCER RISK
Risk from diagnostic x-rays:
• 5 cancer deaths per 100,000 person mGy
~ 0.05% per one 10 mGy CT (1 in 2000)
• Background: ~20% death due to cancer
• Thus, risk of death due to cancer from 10 mGy of
x-rays, averaged over population is 20.05%
• Effective dose for cardiac CT is ~ 10-15 mSv
Commonly accepted risk:
5 cancer deaths per 100,000 person mGy
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Cynthia H. McCollough, PhD: Radiation as a
carcinogen
May 13, 2008- 10:15 AM
RISK ESTIMATION
• Controversial because not all cancer dosedoseresponse curves are linear
• Insufficient data at low doses results in
uncertainty of risk estimates
• Risk estimates apply to populations, not
individuals
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