Ionizing radiation: a risk factor for mesothelioma

Our plain-English summary of Ionizing radiation: a risk factor for mesothelioma, by J.E. Goodman, M.A. Nascarella, P.A. Valberg (Cancer Causes & Control, 2009).

The study

• Authors: J.E. Goodman, M.A. Nascarella, P.A. Valberg
• Journal: Cancer Causes & Control
• Published: 2009;20(8):1237-54
• Type of article: Review
• Cited by: 63 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In the majority of mesothelioma cases worldwide, asbestos is a likely causal factor, but several alternative factors, such as ionizing radiation, have been recognized. We reviewed ionizing-radiation evidence from epidemiology studies of (1) patients exposed to the diagnostic X-ray contrast medium "Thorotrast," (2) patients undergoing radiation therapy (i.e., to treat cancer), and (3) atomic energy workers chronically exposed to lower levels of radiation. The results from these populations are also supported by case reports of mesothelioma following therapeutic radiation. Statistically significant associations were found in many, but not all, epidemiology studies (particularly those of Thorotrast- and radiation-treated patients). Given the low mesothelioma rate in the general population, the consistently increased risk among these radiation-exposed individuals is noteworthy. Many studies were limited by the lack of a uniform manner in which mesothelioma was reported prior to introduction of a uniform classification system (ICD-10). Future studies that rely on ICD-10 should have greater power to detect an association. While the evidence falls short of a definitive causal link, considering studies in which statistical significance was achieved, the case reports, and the plausible mode of action, we conclude that the evidence is supportive of a causal link between ionizing radiation exposure and mesothelioma risk.

In plain English

This article was a review, not a new study. The authors searched PubMed for epidemiology studies of ionizing radiation and mesothelioma in three groups: patients given Thorotrast, a radioactive X-ray contrast medium; patients given radiation therapy, mostly for an earlier cancer; and nuclear industry workers. They also listed published case reports. In a Danish Thorotrast cohort, pleural and peritoneal tumors combined were raised compared with similar unexposed patients (RR = 9.41, 95% CI: 1.05–444.75). In a Dutch study, 13 of 2,567 five-year survivors of Hodgkin's lymphoma developed mesothelioma, and the SIR among those given radiotherapy was 29.4 (95% CI 15.7–50.4). A registry analysis of 1,489,643 cancer patients, with or without radiotherapy, found no statistically significant overall excess of pleural mesothelioma as a second cancer (O/E = 0.88, 95% CI: 0.74–1.04). Worker studies showed fewer statistically significant results; in the 15-country study, the 39 pleural cancers did not reach significance. The authors noted that mesothelioma had no specific disease code before ICD-10, that case numbers were small, and that asbestos may confound worker studies. They concluded the evidence strongly suggests ionizing radiation increases mesothelioma risk.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Literature review of published epidemiology studies and case reports. For some worker studies the authors calculated SMRs and confidence intervals that the original studies did not give.
• Who was studied: Published studies of three groups: Thorotrast-exposed patient cohorts (Denmark, Sweden, Japan, Germany, US, Portugal); patients given radiation therapy for an earlier cancer (SEER and Nordic, Dutch and other registries, and NSABP trials); and nuclear industry and radiation workers (UK, US, France, Russia and a 15-country study). Also published case reports of mesothelioma after radiation therapy.
• Exposure: Ionizing radiation from three sources: Thorotrast, a contrast medium containing radioactive thorium dioxide that emits mostly alpha particles; therapeutic radiation; and occupational X- and gamma radiation and internal radionuclides. Asbestos was discussed only as a possible confounder.
• Main results:
  • Andersson et al. (Danish Thorotrast-treated patients): malignant tumors of the pleura and peritoneum combined were increased compared with the Danish cancer registry (SMR = 8.33, 95% CI: 2.69–19.45) and compared with similar patients not exposed to Thorotrast (RR = 9.41, 95% CI: 1.05–444.75).
  • van Kaick et al. (German cohort of 2,326 Thorotrast-exposed patients and 1,890 controls): four peritoneal and five pleural mesotheliomas occurred in exposed patients and none in controls. No risk ratio was calculated.
  • Cavazza et al. (1,489,643 patients with an earlier cancer in SEER or the Connecticut Tumor Registry, whether or not given radiotherapy): 142 had mesothelioma as a second primary cancer, with no statistically significant overall excess (O/E = 0.88, 95% CI: 0.74–1.04). Only 33 of the 142 had been treated with radiation alone.
  • Hodgson et al. (18,862 five-year Hodgkin's lymphoma survivors): pleural cancer was the largest risk associated with radiation treatment, with 12 cases observed.
  • Teta et al. (SEER lymphoma patients given radiation): mesothelioma risk was raised in men with Hodgkin's lymphoma (4 cases) and in men and women with non-Hodgkin's lymphoma combined (10 cases). There were no cases in women with Hodgkin's lymphoma.
  • De Bruin et al. (2,567 five-year Hodgkin's lymphoma survivors in the Netherlands): 13 developed mesothelioma (SIR 25.7, 95% CI 13.7–44.0 compared with the general population). Among those treated with radiotherapy the SIR was 29.4.
  • Neugut et al. (SEER breast carcinoma patients given radiotherapy): mesothelioma rates were increased, but not significantly.
  • Omar et al. (Sellafield, British Nuclear Fuels): pleural cancer rates were increased in plutonium workers and in workers exposed to other forms of radiation. No pleural cancers were observed in non-radiation workers.
  • Matanoski et al. (US nuclear shipyard workers): compared with US males, the mesothelioma SMR was 5.11 (95% CI: 3.03–8.08) in nuclear workers with 5.0 mSv or more and 2.41 (95% CI: 1.16–4.43) in non-nuclear workers. Internal comparisons by dose were not statistically significant.
  • Cardis et al. (407,391 nuclear industry workers in 15 countries): 39 pleural cancers were reported. The result did not reach statistical significance (excess relative risk per Sv = 5.28, 90% CI below 0.0 to 39.9), and the dose-response relationship was also not significant.
• The authors' conclusion: The authors concluded that the evidence falls short of definitive proof of causality but that the weight of currently available data strongly suggests ionizing radiation increases mesothelioma risk.
• Limitations the authors state:
  • Mesothelioma had no specific disease code before ICD-10, so many studies used pleural cancer as a stand-in, and some cases were likely misclassified.
  • Most studies had very few mesothelioma cases.
  • The long latency of mesothelioma may mean cases were missed in studies with short follow-up.
  • Most worker studies had too few subjects per exposure group to assess dose-response.
  • Asbestos could confound the occupational studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Epidemiology, Statistical Significance.

Related studies

• A nested case-control study of lung cancer risk and ionizing radiation exposure at the portsmouth naval shipyard — J.H. Yiin, S.R. Silver, et al. (2007)
• Risk of cancer from occupational exposure to ionising radiation: retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS) — D.B. Richardson, E. Cardis, et al. (2015)
• Inter-rater agreement for a retrospective exposure assessment of asbestos, chromium, nickel and welding fumes in a study of lung cancer and ionizing radiation — E.A. Seel, D.D. Zaebst, et al. (2007)
• Cancer risks and low-level radiation in U.S. shipyard workers — G.M. Matanoski, J.A. Tonascia, et al. (2008)
• Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database — A. Farioli, M. Ottone, et al. (2016)
• Modulating factors in the expression of radiation-induced oncogenic transformation — E.J. Hall, T.K. Hei (1990)

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