INWORKS study

The INWORKS study is an international epidemiological study of nuclear workers set up in 2011, coordinated by the International Agency for Research on Cancer (IARC) and to which IRSN is contributing. The aim of the study is to improve knowledge of the risks of cancer and non-cancerous diseases associated with protracted exposure to low doses of ionizing radiation delivered at low dose rates.

Background and objectives

The current system for managing worker radiation protection is based on extrapolated knowledge of radiation-induced risks from the epidemiological follow-up of survivors of the 1945 bombings of Hiroshima and Nagasaki (Japan). To date, the validity of this extrapolation for repeated exposure to low doses of radiation has been limited by the small numbers and short follow-up duration of epidemiological studies. The international INWORKS study was initiated to better characterize the relationship between protracted exposure to low doses of ionizing radiation and mortality from cancer and non-cancerous diseases.

INWORKS is the largest epidemiological study ever carried out, aimed at quantifying the health risks potentially associated with repeated exposure to ionizing radiation in an occupational context. The robustness of this study is the result of the protocol put in place, based on the combination of the world's largest cohorts of workers, the standardization of inclusion criteria, the verification of data homogeneity and quality, the application of different statistical analysis methods, and the verification of results stability through sensitivity analyses. The method used to reconstruct individual dosimetric histories has been the subject of a specific publication.

Course of the study

Populations included

INWORKS is based on a protocol identical to that used for the “15-country” study launched by IARC in the 2000s, the results of which have been published since 2005 (Cardis 2005, Cardis 2007, Vrijheid 2007). This study combines data from the three most data-rich cohorts of workers in the “15 countries” study - the French, the British (UK), and the American (USA) - recently expanded and updated.

The INWORKS study includes 309,932 workers and reaches high statistical power in the field of epidemiology of repeated low-dose exposure, since it is based on precise individual data and long-term follow-up, averaging 35 years.

The French cohort includes over 59,000 workers hired for at least one year between 1950 and 1994 by various companies.
The UK cohort is made up of workers hired for at least one year before 2000 by organizations providing dosimetry monitoring data to the National Register of Nuclear Workers.

The U.S. cohort comprises workers hired at least one year before 1993 by the U.S. Department of Energy.
The description of the INWORKS study was the subject of a scientific publication in the International Journal of Epidemiology (Hamra et al. 2015).

Methodology

The reconstitution for each worker of annual absorbed doses (expressed in Gray) to the various organs relevant to the study of the risk of solid cancer, leukemia, or non-cancerous diseases (i.e., colon, lung, bone marrow, and breast in women) was carried out on the basis of individual data collected as part of the regulatory monitoring of workers by applying the dose conversion coefficients of the International Commission on Radiological Protection (ICRP). The methodology used to reconstitute doses is described in an article published in Radiation Research (Thierry-Chef et al. 2015).

Comparison of the doses thus reconstituted with the mortality observed in the cohort leads to an analysis of the risks of death from leukemia, lymphoma, and multiple myeloma, solid cancers and non-cancerous diseases associated with exposure to ionizing radiation:

  • for each cohort, mortality follow-up based on death certificates was carried out (up to 2014 for France, 2012 for the UK, and 2016 for the USA);
  • the excess relative risk (ERR) of death from leukemia (excluding chronic lymphocytic leukemia), lymphoma, and multiple myeloma is estimated using a linear model on cumulative dose, taking into account the effect of country, sex, age, and birth cohort;
  • a latency period of two years for leukemia and 10 years for lymphoma and multiple myeloma is applied;
  • in addition, analyses were carried out on restricted dose intervals;
  • sensitivity analyses were also carried out for certain variables (socio-professional category, length of latency period, neutron exposure, internal contamination).

Results

 

References

  • Leuraud K, Laurier D, Gillies M, Haylock R, Kelly-Reif K, Bertke S, Daniels RD, Thierry-Chef I, Moissonnier M, Kesminiene A, Schubauer-Berigan MK, Richardson DB. Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study. Lancet Haematol. 2024 (https://www.thelancet.com/journals/lanhae/home)
  • Richardson DB, Leuraud K, Laurier D, Gillies M, Haylock R, Kelly-Reif K, Bertke S, Daniels RD, Thierry-Chef I, Moissonnier M, Kesminiene A, Schubauer-Berigan MK. Low dose exposure to ionizing radiation and cancer: Updated findings from the International Nuclear Workers Study (INWORKS). British Med J. 2023; 382:e074520. https://www.bmj.com/content/382/bmj-2022-074520 
  • Hamra GB, Richardson DB, Cardis E, Daniels RD, Gillies M, O’Hagan JA, Haylock R, Laurier D, Leuraud K, Moissonnier M, Schubauer-Berigan M, Thierry-Chef I, Kesminiene A. Cohort Profile: The International Nuclear Workers Study (INWORKS). Int. J. Epidemiol 2015; http://dx.doi.org/10.1093/ije/dyv122.
  • Leuraud K, Richardson DB, Cardis E, Daniels RD, Gillies M, O’Hagan JA, Hamra GB, Haylock R, Laurier D, Moissonnier M, Schubauer-Berigan M, Thierry-Chef I, Kesminiene A. Ionizing Radiation and Leukaemia and Lymphoma: Findings from an international cohort study of radiation-monitored workers (INWORKS). The Lancet Haematol. 2015 July; 2: e276-e281. http://dx.doi.org/10.1016/S2352-3026(15)00094-0.
  • Thierry-Chef I, Richardson DB, Daniels RD, Gillies M, Hamra GB, Haylock R, Kesminiene A, Laurier D, Leuraud K, Moissonnier M, O’Hagan JA, Schubauer-Berigan M, Cardis E, on Behalf of the INWORKS Consortium. Dose estimation for a study of nuclear workers in France, the United Kingdom and the United States of America: methods for the International Nuclear Workers Study (INWORKS). Radiat. Res. 2015; 183(6):632-642.

Features

Dates : 2011-2024

Partners :

International Agency for Research on Cancer (IARC)
National Institute for Occupational Safety and Health (NIOSH)
UK Health Security Agency (UK HSA)
University of California Irvine (UCI)
Barcelona Institute for Global Health (ISGlobal)

IRSN laboratory involved :
Laboratoire d'épidémiologie des rayonnements ionisants (Lepid)