Literature Scan
Exposure to Ionizing Radiation and Leukemia
Risk: Is There a Safe Threshold?
Exposure to high doses of radiation is rare outside of radiation
therapy, but repeated or protracted low-dose exposure from
occupational and environmental
sources has become more common over the last 25 years. The
average yearly dose of radiation
has increased from 0.5 mGy in
1982 to 3.0 m/Gy in 2006, largely
due to a rise in medical radiation exposure.1 Because ionizing
radiation is a carcinogen linked
to cancer development, its use
in medical practice must be
balanced against the associated
health risks.
While most previous studies
have examined cancer-associated
mortality risk among people
who have been exposed to high
levels of radiation, there is
little information on this risk for
people exposed to repeated and
prolonged low-dose exposure. In
an analysis of the International
Nuclear Workers Study (INWORKS), Klervi Leuraud, PhD,
from the Institute for Radiological Protection and Nuclear Safety
at Fontenay aux Roses in Cedex,
France, and colleagues looked
specifically at development of
hematologic malignancies among
workers from France, the United
Kingdom, and the United States
who were exposed to low-dose
protracted or intermittent radiation.
According to the findings,
even low accrued doses of radiation (<5 mGy) had an excess risk
of leukemia-related mortality,
suggesting that the potential
threshold below which radiation
is harmless should be very low.
All participants in the INWORKS study had been monitored for external exposure to
radiation with personal dosimeters and were followed for up to
60 years after exposure. Workers
were employed for at least one
year at one of the following sites:
the Atomic Energy Commission,
AREVA Nuclear Cycle, or the
National Electricity Company
in France; the Departments of
Energy and Defense in the United
States; and nuclear industry employers included in the National
Registry for Radiation Workers in
the United Kingdom. Data were
available from 1944 through 2005.
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ASH Clinical News
Overall, data from 308,297
radiation-monitored participants
were analyzed. Participants were
followed for 8.22 million personyears to assess deaths up to 2004
in France, 2001 in the United
Kingdom, and 2005 in the United
States. Causes of death were
ascertained from the participants’
death certificates and coded
according to the International
Classification of Diseases.
Data on ionizing radiation
were extracted from dose registry,
government, and company records, which provided individual
yearly estimates of whole-body
exposure to external radiation.
Dr. Leuraud and colleagues quantified the associations between the
estimated radiation dose absorbed
by bone marrow and leukemia,
lymphoma, and myeloma mortality.
Participants were followed
for a mean of 27 years, and 22
percent of the workers (n=66,632)
were deceased at the time of
follow-up.
Radiation doses were accrued
at “very low rates” among individuals (mean = 1.1 Gy per individual per year). Among the total
INWORKS population, the mean
cumulative dose was 15.9 mGy:
11.6 mGy in French workers; 15.2
mGy for U.S. workers; and 18.2
mGy for U.K. workers.
Leukemia (excluding chronic
lymphocytic leukemia [CLL]) was
the reported cause of death in 538
individuals, lymphoma in 814 individuals, and multiple myeloma
in 293 individuals.
Notably, of the deaths caused
by leukemia excluding CLL, more
than half (53%; n=281) occurred
in people who had accrued a
mean of less than 5 mGy of radiation exposure. As seen in TABLE
2, the excess relative risk (ERR)
of leukemia mortality was 2.96
per Gy (90% CI 1.17-5.21), “most
notably because of an association between radiation dose and
mortality from chronic myeloid
leukemia (CML; ERR=10.45/Gy;
90% CI 4.48-19.65).
The researcher s also detected
positive associations between
cumulative dose and the excess
relative risk of acute myeloid
leukemia (AML; ERR=1.29;
90% CI –0.82 to 4.28) and acute
lymphocytic leukemia (ALL;
ERR=5.80; 90% CI NE to 31.57).
Associations for Hodgkin lymphoma (ERR=2.94; 90% CI NE
to 11.49), non-Hodgkin lymphoma (ERR=0.47; 90% CI –0.76
to 2.03), and multiple myeloma
(ERR=0.84; 90% CI –0.96 to 3.33)
were also observed, but were not
as strong. Dr. Leuraud and colleagues also observed a negative
association between radiation and
development of CLL (TABLE 2).
“This study provides strong
evidence of positive associations
between protracted low-dose
radiation exposure and risk of
developing leukemia,” the authors
concluded, adding that current
radiation protection systems are
based on a model derived from
acute exposures, and assume that
the risk of leukemia progressively
diminishes at lower doses and dose
rates. “Our results provide direct
estimates of risk per unit of protracted dose in ranges typical of
environmental, diagnostic medical, and occupational exposure.”
Because radiation dose estimates are prone to measurement
error, exposure misclassification
was an unavoidable study limitation. “Outcome misclassification
is also a potential concern in
studies that rely on death certificates for classification of leukemia
and lymphoma by subtype,” the
authors noted.
The analysis also did not account for potential confounders
of the associations being studied,
including participants’ smoking
status or exposure to other known
causes of leukemia. In the future,
Dr. Leuraud and colleagues
added, similar studies should be
conducted specifically among
medical workers to examine their
radiation-related risk. ●
REFERENCES
1. Mettler FA Jr, Thomadsen BR, Bhargavan M, et al.
Medical radiation exposure in the U.S. in 2006:
preliminary results. Health Phys 2008;95:502-7.
2. Leuraud K, Richardson DB, Cardis E, et al. Ionising
radiation and risk of death from leukaemia and
lymphoma in radiation-monitored workers (INWORKS):
an international cohort study. Lancet Haemotol.
2015;2:e276-e281.
Excess Relative Risk per Gy of Cumulative Red Bone Marrow Dose
for Causes of Death
TABLE 2.
Deaths
Excess Relative
Risk per Gy
90% confidence
interval
Leukemia (excluding chronic
lymphocytic leukemia)
531
2.96
1.17-5.21
Chronic myeloid leukemia
100
10.45
4.48-19.65
Acute myeloid leukemia
254
1.29
−0.82 to 4.28
Acute lymphocytic leukemia
30
5.80
NE-31.57
Chronic lymphocytic leukemia
138
−1.06
NE-1.81
Multiple myeloma
293
0.84
−0.96 to 3.33
Non-Hodgkin lymphoma
710
0.47
−0.76 to 2.03
Hodgkin lymphoma
104
2.94
NE-11.49
NE=not estimable
November 2015