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Site-specific Solid Cancer Mortality After Exposure to Ionizing Radiation: A Cohort Study of Workers (INWORKS)

Richardson, David, B.a; Cardis, Elisabethb–d; Daniels, Robert, D.e; Gillies, Michaelf; Haylock, Richardf; Leuraud, Klervig; Laurier, Dominiqueg; Moissonnier, Monikah; Schubauer-Berigan, Mary, K.e; Thierry-Chef, Isabelleh; Kesminiene, Ausreleh

doi: 10.1097/EDE.0000000000000761

Background: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer.

Methods: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation–mortality associations were estimated using a maximum-likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association.

Results: The analysis included 17,957 deaths attributable to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum-likelihood method to quantify associations between radiation dose- and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types, the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization.

Conclusions: The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

From the aDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC; bCenter for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; cUniversitat Pompeu Fabra (UPF), Barcelona, Spain; dCIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; eNational Institute for Occupational Safety and Health, Cincinnati, OH; fPublic Health England Centre for Radiation, Chemical and Environmental Hazards (PHE-CRCE), Chilton, United Kingdom; gInstitut de Radioprotection et de Sûreté Nucléaire (IRSN), Fontenay-aux-Roses, France; and hInternational Agency for Research on Cancer, Lyon, France.

Submitted December 17, 2016; accepted September 27, 2017.

Supported, partly, by the US Centers for Disease Control and Prevention (RO3 OH010056) and Ministry of Health, Labour and Welfare of Japan (grant number 2012-02-21-01). The French cohort was coordinated by Institut de Radioprotection et de Sûreté Nucléaire, with part funding from AREVA and EDF. US funding was provided by the National Institute for Occupational Safety and Health, US Department of Energy through an agreement with the US Department of Health and Human Services and a grant received by the University of North Carolina from the National Institute for Occupational Safety and Health (R03 OH010056). The UK cohort was coordinated by Public Health England who operates the UK’s National Registry for Radiation Workers.

K.L. and D.L. report other support from AREVA and from EDF, during the conduct of the study. R.D.D. and M.K.S.-B. report other support from the US Department of Energy during the conduct of the study. D.B.R. reports grants from the US Centers for Disease Control and Prevention during the conduct of the study. The other authors have no conflicts to report.

The findings and conclusions in this report are those of the authors and do not necessarily represent views of the National Institute for Occupational Safety and Health.

Availability of data: This study’s data are not freely available. For reasons of ethics and permissions from different agencies, the data are maintained at the International Agency for Research on Cancer (Lyon, France); further, it is not possible to send the data outside of the agency.

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Correspondence: David Richardson, Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail:

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