The Lancet Haematology Jul 2015 Volume 2 Number e267-e306 http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026%2815%2900094-0/abstract free full text pdf – see original link.
Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS): an international cohort study
Klervi Leuraud, David B Richardson, Elisabeth Cardis, Robert D Daniels, Michael Gillies, Jacqueline A O’Hagan, Ghassan B Hamra, Richard Haylock,
Dominique Laurier, Monika Moissonnier, Mary K Schubauer-Berigan, Isabelle Thierry-Chef, Ausrele Kesminiene
Background There is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified
associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA.
Methods We assembled a cohort of 308 297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8·22 million person years.
We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality.
Findings Doses were accrued at very low rates (mean 1·1 mGy per year, SD 2·6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2·96 per Gy (90% CI 1·17–5·21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10·45, 90% CI 4·48–19·65).
Interpretation This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia.
Funding Centers for Disease Control and Prevention, Ministry of Health, Labour and Welfare of Japan, Institut de Radioprotection et de Sûreté Nucléaire, AREVA, Electricité de France, National Institute for Occupational Safety and
Health, US Department of Energy, US Department of Health and Human Services, University of North Carolina, Public Health England.
Copyright © Leuraud et al. Open Access article distributed under the terms of CC BY-NC-ND.
Although exposure to high-dose ionising radiation is rare
outside of radiotherapy, repeated or protracted low-dose
exposure has become increasingly common over the past
25 years.1 Occupational and environmental sources of
radiation exposure are important; however, the largest
contributor to this trend is medical radiation exposure.
In 1982, the average yearly dose of ionising radiation
from medical exposures was about 0·5 mGy per person
in the USA; by 2006, it had increased to 3·0 mGy.2
A similar pattern exists in other high-income countries:
use of diagnostic procedures involving radiation in the
UK more than doubled over that period3 and more than
tripled in Australia.4 Because ionising radiation is a
carcinogen,5 its use in medical practice must be balanced
against the risks associated with patient exposure.6
The primary basis for estimating cancer risks from
ionising radiation exposures are epidemiological studies
of Japanese survivors of the atomic bombings of
Hiroshima and Nagasaki in August, 1945.7 Within a few
years of the bombings there was evidence of an excess of
leukaemia, predominantly myeloid subtypes, among the
survivors.8–12 These fi ndings helped to establish that
ionising radiation causes leukaemia.13 However, this
evidence mostly relates to acute high-dose exposure. The
risks associated with protracted or repeated low-dose
exposures are more relevant to the public and health
The International Nuclear WORKers Study
(INWORKS) was done to strengthen the scientifi c basis
for protecting people from low-dose protracted or
intermittent radiation exposure. It included workers
from France,14 the UK,15 and the USA16 who have been
monitored for external exposure to radiation with
personal dosimeters and followed up for up to 60 years
after exposure. Here, we report data for leukaemia,
lymphoma, and multiple myeloma mortality among
participants of INWORKS.
Research in context
Evidence before this study
Ionising radiation causes leukaemia. The primary quantitative
basis for radiation protection standards comes from studies of
populations exposed to acute, high doses of ionising radiation.
Although previous studies of nuclear workers addressed
leukaemia radiogenicity, questions remain about the size of the
risk from protracted radiation exposure in occupational settings.
Added value of this study
We report a positive dose–response relationship between
cumulative, external, protracted, low-dose exposure to ionising
radiation, and subsequent death caused by leukeamia (excluding
chronic lymphocytic leukaemia). The risk coeffi cient per unit dose
was consistent with those derived from analyses of other
populations exposed to higher radiation doses and dose rates.
Implications of all the available evidence
The present study provides strong evidence of a positive
association between radiation exposure and leukaemia even for
low-dose exposure. This finding shows the importance of
adherence to the basic principles of radiation protection—to
optimise protection to reduce exposures as much as reasonably
achievable and—in the case of patient exposure—to justify that
the exposure does more good than harm.
Study design and participants
The INWORKS cohort consists of nuclear workers from
three of the major partners included in the previously
published 15-country study of cancer among workers in
the nuclear industry:17 France,14 the UK,15 and the USA.16
Less than 20% of deaths from leukaemia were contributed
by the other 12 countries.18 These cohorts have been
updated since the 15-country study. INWORKS includes
fewer partners than the earlier 15-country study because
of the limited resources and the consequent need for
effi ciency in project coordination.
The study includes workers employed by the French
Atomic Energy Commission, AREVA Nuclear Cycle, and
Electricité de France, workers employed by the British
Atomic Weapons Establishment, British Nuclear Fuels,
the UK Atomic Energy Authority, British Energy
Generation, the UK Ministry of Defence, and other
organisations providing data to the National Registry for
Radiation Workers, and workers employed by the US
Department of Energy’s Hanford Site, Savannah River
Site, Oak Ridge National Laboratory, Idaho National
Laboratory, and the Portsmouth Naval Shipyard. Workers
who were employed in the nuclear industry for less than
1 year were excluded. In France, workers were given the
opportunity to refuse participation, which is required by
the French Data Protection Authority; however, none did.
In the USA, worker information was taken from existing
records, with no direct contact with any participants;
because there is minimal risk to participants, the
National Institute for Occupational Safety and Health
institutional review board waived requirements for
informed consent. UK workers can refuse to participate
in the National Registry for Radiation Workers and
associated studies; less than 1% did.
Participants were followed up for a total of 8·22 million
person-years to ascertain vital status up to 2004 in France,
2001 in the UK, and 2005 in the USA. Underlying cause
of death was abstracted from death certifi cates and
investigate the potential for an increased cancer risk in
relation to radiation exposure, one-sided p values and
corresponding 90% CIs are usually presented; we follow
that convention here by reporting 90% CIs. All models
were fi tted with EPICURE software.23
Role of the funding source
The funders had no role in study design, data analysis,
data interpretation, or writing of the report. AREVA and
Électricité de France provided historical occupational
data and individual monitoring data for part of the
French cohort. KL, DBR, and MM had full access to all
the data in the study. KL and DBR had fi nal responsibility
for the decision to submit for publication.
We assembled a cohort of 308 297 radiation-monitored
workers. Table 1 shows the characteristics of the study
population. Mean follow-up was 27 years (SD 12) and
nearly 22% of the workers were deceased at the end of
follow-up. Mean cumulative dose was 16 mGy. The median
was 2·1 mGy (IQR 0·3–11·7), with a tenth percentile of
0·0 mGy and a 90th percentile of 40·8 mGy (appendix p 1).
The mean yearly dose was 1·1 mGy (SD 2·6).
We recorded 531 deaths caused by leukaemia excluding
CLL, 814 caused by lymphoma, and 293 caused by multiple
myeloma. 281 (53%) of 531 deaths caused by leukaemia
excluding CLL occurred in people who had accrued less
than 5 mGy (appendix p 3). The RR of death caused by