Risk of cancer from occupational exposure to ionising radiation: retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS)

We thank Scott (1), Uzoigwe (2), and Doss (3) for their interest in our study of cancer among radiation-monitored nuclear workers in France, the UK, and the USA (4).

Scott questioned lagging cumulative radiation dose assignment in our analysis of solid cancer mortality. Scott wrote that “If the cancer death occurred long after ending employment, then there is no scientific justification for throwing away any radiation dose accumulated while being employed long before cancer occurrence.” We can confirm that the method of exposure lagging used does not throw away radiation dose accumulated long before cancer occurrence. Rather, in our analysis the lag discounts exposures that occurred in the years immediately prior to death. Lagging exposure assignment is common practice in cancer mortality studies, and is an analytical approach to account for some delay between exposure and response due to induction, latency, and cancer morbidity preceding death.

Uzoigwe questioned use of a linear model in our analyses. Uzoigwe wrote “It is premature to a priori assume there is no such hormetic phenomenon and confine the data to a single-tailed statistical evaluation.” We can assure that we did not simply assume a linear model. We examined the relative rate of cancer across categories of cumulative dose, observed that the trend in the excess relative rate of cancer excluding leukemia with dose was well described by a linear function of cumulative dose, and noted that a higher order polynomial function of dose did not substantially improve the model fit. Rather than confining ourselves to evaluation of a one-sided hypothesis, we instead focused on estimation of associations and their precision. We noted that the bounds of the reported 90% confidence interval for the estimated association correspond to a critical value for a one sided hypothesis, such that significance at 0.05 level is obtained when the interval does not include 0.

Doss contended that a major flaw in our analyses is the absence of information on doses from medical procedures which, on a population level, varied over time. Most epidemiological cohort studies of cancer outcomes lack detailed individual information on medical radiation doses. As detailed in our report, however, our analysis was adjusted for attained age, birth cohort, and their product. This yields adjustment for confounding of our results by these temporal factors; we examined associations between individually-monitored occupational doses and these adjusted cancer rates in our analyses.

Sincerely,

David B Richardson1
associate professor
Elisabeth Cardis2,3,4
group head, professor, senior investigator
Robert D Daniels5
senior investigator
Michael Gillies6
senior investigator
Jacqueline A O’Hagan6
group leader
Ghassan B Hamra7
assistant professor
Richard Haylock6
senior investigator
Dominique Laurier8
group head
Klervi Leuraud8
investigator
Monika Moissonnier9
senior programmer
Mary K Schubauer-Berigan5
senior investigator
Isabelle Thierry-Chef9
researcher
Ausrele Kesminiene9
group leader

1 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
2 Center for Research in Environmental Epidemiology, Barcelona, Spain
3 Universitat Pompeu Fabra, Barcelona, Spain
4 CIBER Epidemiología y Salud Pública, Madrid, Spain
5 National Institute for Occupational Safety and Health, Cincinnati, OH, USA
6 Public Health England Centre for Radiation, Chemical and Environmental Hazards, Chilton, UK
7 Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, PA, USA
8 Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France
9 International Agency for Research on Cancer, Lyon, France

REFERENCES
(1) Scott BR. Re: Risk of cancer from occupational exposure to ionising radiation: retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS). BMJ 2015;351:h5359/rr-1.
(2) Uzoigwe CE. INWORKS Radiation Studies: Asking the right question? BMJ 2015;351:h5359/rr-0.
(3) Doss M. INWORKS study does not provide evidence for increase in solid cancers from protracted exposure to low doses of ionising radiation. BMJ 2015;351:h5359/rr.
(4) Richardson DB, Cardis E, Daniels RD, Gillies M, O'Hagan JA, Hamra GB, Haylock R, Laurier D, Leuraud K, Moissonnier M, Schubauer-Berigan MK, Thierry-Chef I, Kesminiene A. Risk of cancer from occupational exposure to ionising radiation: retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS). BMJ. 2015 Oct 20;351:h5359.