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INWORKS: Cancer mortality after low dose exposure to ionising radiation in workers

A recent epidemiological study published in the British Medical Journal, titled “Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study”, evaluated the effects of long-term exposure to low-dose ionizing radiation on cancer mortality. This study by Richardson et al. (2023) is an update of previous work, discussed below.

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History of the INWORKS studies

The INternational WORKers Study (INWORKS) is an international study that combines cohorts of nuclear workers in France, the United Kingdom, and the United States. INWORKS is one of the largest, most statistically robust mortality studies. Overall, the study includes 309,932 workers, of which 40,445 are women (~13%). A detailed description of the INWORKS cohorts can be found in Hamra et al. (2016).

The INWORKS studies were born out of an earlier 15-country study, which included Canada, on the mortality of nuclear energy workers (Cardis et al., 2007). Within the 15-country study, the cohorts from France, the United Kingdom, and the United States were selected for the series of subsequent INWORKS studies because they were the most informative: their data had been recently updated, they provided over half of the person-yearsFootnote 1 of follow-up, and they included most of the cancer and leukemia deaths.

Those INWORKS studies investigated the relationship between exposure to ionizing radiation and cause-specific risk of death from:

Overall, these studies found strong evidence of positive associations between chronic low-dose radiation exposure and risk of death from leukemia, all solid cancers combined, many site-specific solid cancers (the most common being lung, prostate, and colon), and non-cancer causes (circulatory diseases primarily). Risk of death increased with cumulative dose for all solid cancers combined.

Summary of the 2023 INWORKS study

The 2023 INWORKS study (Richardson et al., 2023) is an update of the 2015 study (Richardson et al., 2015); both studies investigated the association between chronic, low dose exposure to ionizing radiation and dying from solid cancer (i.e., all solid cancers combined, but not cancers that develop in the blood, bone marrow, or lymph nodes). According to the 2023 INWORKS study, the risk of radiation-induced solid cancer mortality resulting from chronic exposure to low doses of radiation may be slightly higher than previously reported. The study supports a linear association between prolonged low-dose external exposure to ionizing radiation and solid cancer mortality.

Limitations of the 2023 INWORKS study

The authors acknowledge that, like all studies, the 2023 INWORKS study has limitations. For example, only external exposures were considered; doses from internal exposures, such as inhalation and ingestion, were excluded. As a result, the risk may be overestimated. This study used effective dose (whole body and estimated dose to the colon) rather than absorbed dose to the organ, which would have provided more precise risk estimates. This study also lacks individual-level data on risk factors, such as smoking, that could affect the radiation–cancer association; therefore, indirect methods were used to assess confounding by smoking. Despite its limitations, the study incorporates one of the more relatively robust methodologies in the field of radiation epidemiology with worker cohorts and provides reasonable risk estimates.

Results from INWORKS (2015, 2023) are comparable to Life Span Study results

The general understanding of radiation-induced risk was first established from the long-standing Life Span Study (LSS) of the atomic bomb survivors, who have been studied since 1958. The atomic bomb survivors received a single, acute (short-term), whole-body exposure to relatively high levels of ionizing radiation. The doses in the LSS are different than the chronic (long-term), low dose exposures experienced by nuclear energy workers.

The INWORKS studies add to our understanding of radiation risk and are more comparable to modern workers than the LSS given the chronic low dose exposures, actual individual dose measurement (rather than estimation), and the detailed follow-up of workers.

The relationship between ionizing radiation and solid cancer mortality in the 2023 INWORKS study is slightly higher than, albeit comparable to, the LSS results (Richardson et al., 2023; Ozasa et al., 2012; Brenner et al., 2022). Results are statistically comparable because the confidence intervals overlap (see table 1). Compared to the previous analysis on solid cancer mortality (Richardson et al., 2015), the 2023 INWORKS study includes more data, with follow-up extended by 10 years, resulting in more precise risk estimates (i.e., a tighter gap between the lower and upper bounds of the confidence intervals). Compared to the LSS analysis on solid cancer mortality, which has 3.1 million person-years of follow-up data, the 2023 INWORKS study has 10.7 million person-years of follow-up data.

Table 1. Comparison of INWORKS and LSS solid cancer mortality results
Study Excess relative risk1 per Gy
(% confidence interval)*
INWORKS (Richardson et al., 2015) 0.47 (90% CI: 0.18, 0.79)
INWORKS (Richardson et al., 2023) 0.52 (90% CI: 0.27, 0.77)
Life Span Study (Ozasa et al., 2012) 0.37 (90% CI: 0.17, 0.60)
Life Span Study (Brenner et al., 2022) 0.44 (95% CI: 0.35, 0.54)

1The rate of disease in an exposed population divided by the rate of disease in an unexposed population, minus 1, expressed as the excess relative risk (ERR) per unit dose (e.g., per gray or per sievert). An ERR of 0.47 per Gy (equivalent to 1 Sv or 1,000 mSv) means that the probability of an individual dying from a radiation-induced cancer is 1.47 times higher for an individual exposed to 1 Gy compared to an unexposed individual.

*A 90% confidence interval (CI) indicates how often (i.e., 90 out of 100 times) the estimated results fall between the upper and lower bounds, while a 95% confidence interval implies a 5% greater certainty.

Epidemiological studies inform national radiation protection

Epidemiological studies such as the INWORKS studies that look at worker health over their entire careers improve our understanding of the risks associated with exposure to low doses of radiation. Most epidemiological studies show a linear relationship between radiation dose and cancer risk, informing the shape of the dose-response curve.

A linear-non-threshold (LNT) model is the dose-response curve used internationally by most health agencies and nuclear regulators, including the CNSC, to set dose limits for workers and members of the public. This is a conservative approach to account for any uncertainties around how exposure to low doses of radiation may affect health outcomes. Further, current average doses to Canadian nuclear workers are far below dose limits as licensees must keep doses to workers as low as reasonably achievable (ALARA), with social and economic factors being considered. Regulatory dose limits are in place to reduce the risk of cancer, which is a stochastic effect (i.e., a health effect that occurs with a probability that is proportional to the dose magnitude).

INWORKS studies will inform the international radiation protection framework

The 2023 INWORKS study results will inform discussions on radiation protection among the international community (e.g., the International Commission on Radiological Protection, or ICRP) on risk assessment in low dose and low-dose rate settings.

The ICRP aims to publish the next set of general recommendations, which will include dose limits, in the early 2030s. The ICRP will consider all relevant studies published in the literature, including this 2023 INWORKS study, when drafting its next set of recommendations.

Conclusion

There is no immediate action needed in response to the 2023 INWORKS study. The study results continue to support the use of the LNT model as a suitable tool for establishing radiation dose limits that align with the international radiation protection framework and the CNSC’s robust regulatory framework for ensuring the health and safety of people and the protection of the environment. The results of the 2023 INWORKS study, combined with other studies on nuclear workers and other radiation-exposed populations, such as medical patients and members of the public, add to the weight of evidence of our understanding of the health effects from low doses of radiation.

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