Radiation Protection Dosimetry Advance Access published March 22, 2015 Radiation Protection Dosimetry (2015), pp. 1–5
doi:10.1093/rpd/ncv037
ON THE ESTIMATION OF RADIATION-INDUCED CANCER RISKS FROM VERY LOW DOSES OF RADIATION AND HOW TO COMMUNICATE THESE RISKS So¨ren Mattsson* and Mats Nilsson Medical Radiation Physics, Department of Clinical Sciences Malmo¨, Lund University, Ska˚ne University Hospital Malmo¨, Malmo¨ SE-205 02, Sweden *Corresponding author: [email protected]
INTRODUCTION
CANCER RISK ESTIMATES AT LOW DOSES
It is important to have good knowledge about the effects of low and very low doses (1 – 100 mSv) of radiation in order to make accurate judgements and trade-offs in a number of areas in society. These include the increasing use of diagnostic radiology, particularly computed tomography (CT), screening tests for cancer, positron emission tomography (PET), PET/CT and fluoroscopically guided complex interventions; the future of nuclear energy production and investments in nuclear technology; occupational radiation exposure; risks for flight personnel; remediation of radon and radon daughters and planning to face the consequences of nuclear and radiological accidents and disasters. After low absorbed doses (10 – 100 mSv), no acute harmful tissue effects are seen(1) and for cancer effects, there is a lack of knowledge due to the absence of statistical power as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. For very low absorbed doses (1 – 10 mSv), the possibility to get information from epidemiology is even more limited(2 – 4). The aim of this article is to review the current knowledge on cancer risks from low and very low absorbed doses (1 – 100 mSv) of ionising radiation and to discuss ways to inform about these risks.
Survivors from Hiroshima and Nagasaki—The Life Span Study cohort, Japan The most informative set of data on the effects of whole body exposures of high-dose-rate gamma radiation (with a small contribution from neutrons) comes from studies of the over 100 000 survivors (including 30 000 children) of the detonations of nuclear weapons over the cities of Hiroshima and Nagasaki in Japan in 1945, the so-called Life Span Study (LSS). The advantages of the LSS are the wide dose range, wide range in age at exposure and long-term followup(2, 5 – 8). The LSS is often described as a high-dose study, but the mean dose in the exposed LSS cohort is only 200 mSv ranging from 5 mSv to 2 –4 Sv. More than half of the exposed individuals received doses ,50 mSv(3, 5). In the latest LSS cohort mortality report (9), there is no indication that the slope of the dose –response curve for solid cancers over the low-dose range restricted to survivors with dose estimates lower than 120 mSv differs significantly from that for the full range and there was no evidence for a threshold. Minimum latency periods of 2– 5 y were apparent for leukaemia (except for chronic lymphocytic leukaemia), but were longer for solid tumours. Excess risk persisted throughout life for most malignancies. For
# The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://rpd.oxfordjournals.org/ at Seton Hall on April 1, 2015
The article is intended to give a short overview of epidemiological data on cancer risks associated with very low absorbed doses of ionising radiation. The linear no-threshold (LNT) approach to estimate cancer risks involves the use of epidemiological data at higher doses (>100 mSv), but is supported by data from lower exposure of more sensitive population groups like fetuses and children and the presence of rare types of cancer. The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with a dose and dose-rate effectiveness (reduction) factor (DDREF) of 2 for extrapolation from high doses, should be used. The numerical value of the DDREF is challenged by the findings from some recent epidemiological studies demonstrating risks per unit dose compatible with the risks observed in the higher dose studies. In general there is very limited knowledge about the cancer risk after low absorbed doses (10 –100 mSv), as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. Even if there may be significant deviations from linearity in the relevant dose range 0– 100 mSv, one does not know the magnitude or even the direction of any such deviations. The risks could be lower than those predicted by a linear extrapolation, but they could also be higher. Until more results concerning the effects of low-dose exposure are available, a reasonable radiation protection approach is to consider the risk proportional to the dose.
S. MATTSSON AND M. NILSSON
cancer incidence (and cancer mortality), the dose– response relationship may be described in various ways; by a linear or a curvilinear function. The results also show substantial differences in the risk of cancer for various organs/tissues. A detailed fit of the dose– response curve to the experimental points shows a fine structure which indicates a greater complexity than described by a linear or simple curvilinear function. Patients having received radiation therapy or multiple X-ray examinations
Studies of in utero X rays and cancer risks in offspring In utero diagnostic X rays (mainly pelvimetry) were linked to an excess of paediatric cancer mortality in offspring as first reported by Stewart et al.(14, 15) already in 1956 and later confirmed(16). In 1997 Doll and Wakeford(17) concluded that irradiation of the fetus in utero increases the risk of childhood cancer with about 6 % per Sv at doses of the order of 10 mSv.
Environmental exposures (radon and radon daughters in houses and workplace, Chernobyl fallout, etc.) Radon, particularly in combination with smoking, constitutes an important public health risk(23). In a collaborative analysis of data from 13 European case– control studies it was concluded that the increase in lung cancer was 16 % (5–31 %) per 100 Bq m23 increase in radon concentration. The dose–response relation seemed to be linear with no threshold and remained significant ( p ¼ 0.04) in analyses limited to individuals from homes with measured radon concentration ,200 Bq m23. In the absence of other causes of death, the absolute risks of lung cancer by age 75 y at usual radon concentrations of 0, 100 and 400 Bq m23 would be 0.4, 0.5 and 0.7 %, respectively, for lifelong non-smokers, and about 25 times greater (10, 12 and 16 %) for cigarette smokers(23). After Chernobyl and among the residents of Belarus, Russia and Ukraine more than 6000 cases (up to the year 2005) of thyroid cancer have been reported in those who were internally exposed to radioactive iodine as children and adolescents at the time of the accident, and more cases can be expected(24).
Occupationally exposed persons These groups include medical staff (radiographers and radiologists), aircraft crews, radium workers, especially instrument dial painters, miners, Chernobyl accident emergency and recovery workers, participants in nuclear weapons tests, and workers in the nuclear weapons and power industries(18). Underground miners have generated estimates of lung cancer risk from radon and its daughters. Radium dial painters have shown a clear
Risk from paediatric CT There are two recent publications. One is a follow-up study of 180 000 young people (0–21 y old) who had CT scans in the UK during 1985–2002. It shows an increase in risks of leukaemia and brain cancer with an increase in doses of radiation from a previous CT scan and gave provisional risk estimates for these two cancers(25).
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Secondary cancers that develop after radiation therapy for cancer(10) and in earlier days also for benign conditions(11) mainly affect the part of the body that was treated. In general, the lifetime risk of a secondary cancer is highest in people treated for cancer as children or adolescents. The dose–response patterns for cancer risks associated with high-dose fractionated radiotherapy are generally similar to those of the atomic bomb survivors, but the risk per Sv is lower for patients treated with high-dose fractionated external radiotherapy compared with that for atomic bomb survivors, likely due to a higher degree of cell killing in the patient group(10). Follow-up of individuals treated as children (0–1.5 y) for childhood skin haemangiomas with low-dose radiotherapy has shown significantly increased numbers of tumours in the central nervous system, thyroid and other endocrine glands (pituitary and parathyroid glands), and breast(12). In studies of patients having undergone repeated fluoroscopic imaging examinations for tuberculosis, there is a significant dose–response association with breast cancer, but not with lung cancer(13). There are also limited data suggesting a possible risk of chronic myeloid leukaemia.
excess of bone cancer arising from large intake of radium. Nuclear workers have experienced radiation dose-related incidence and mortality risk increases for leukaemia (excluding chronic lymphocytic leukaemia). In the UK, incidence was slightly more elevated (ERR per Sv, 1.7; 90 % CI, 0.06–4.3) than the dose-associated risks of the atomic bomb survivors (ERR per Sv, 1.4; 90 % CI, 0.1–3.4)(19). These workers also had statistically significant increases for all cancers combined other than leukaemia. Dose-associated increases were also apparent for lung cancer in a 15-country study, although the associations with lung cancer may have been confounded by smoking(20). Recently, a statistical association was reported between chromosome translocation frequencies in cultures of peripheral blood lymphocytes and increasing radiation dose score based on numbers and types of diagnostic X-ray examinations in a cohort of US radiological technologists(21). Valuable information on significant long-term effects from low-dose exposures to internally incorporated radionuclides has been provided by epidemiological studies of the health of workers from the Mayak nuclear complex in the Southern Urals of Russia(22).
CANCER RISKS FROM LOW DOSES OF RADIATION
Biophysical argument for linearity The possible cancer risks caused by ionising radiation doses of 100 mSv or less are too small to be estimated directly from epidemiological data involving all age groups and all cancers even in a large population group. The linear no-threshold (LNT) approach to estimate such risks involves the use of epidemiological data at higher doses, but is supported by data from exposure of more sensitive groups like fetuses and children and the presence of rare types of cancer, establishing an ‘anchor point’ for the linear model, around 6 –10 mSv(29). For the type of X rays used, 6 –10 mSv means an average of around one-hit per cell. Based on the single-cell hit theory, it is therefore likely that half the dose gives half the risk and so on. At lower doses than 6–10 mSv these arguments speak for linearity down to very low doses(29). Summary of cancer risk estimates at low doses The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with an uncertain dose and dose-rate effectiveness (reduction) factor (DDREF) of two for extrapolation from high doses, is a prudent basis for radiation protection at low doses and low dose rates. The numerical value of the DDREF is challenged by the findings from recent epidemiological studies demonstrating risks compatible with the risks observed in the higher dose studies(2). There is evidence that a small risk of cancer results from low-level exposure to radiation and that the excess risk is around that predicted by current risk models (Table 1). More open is an issue how different cancer types respond to radiation. Because the results of human epidemiology studies as well as radiation effects on animals and cell
Table 1. Nominal probability coefficients for cancer after exposure to radiation at low dose and dose rate. Probability of fatal cancer, % per Sv Year of the estimate Entire population Adults only
1990(30) 7.3 5.6
2007(2) 5.7 4.2
In Publ 103(2) the estimate is based on cancer incidence weighted for lethality and life impairment, whereas in Publ 60(30) the estimate is based on fatal cancer risk weighted for non-fatal cancer, relative life lost for fatal cancers and life impairment for non-fatal cancer.
cultures may be interpreted differently, variations in published relative risk values are seen. ICRP and many other authors use an average value of 5 % per Sv as an approximated overall detriment coefficient. There continues to be no direct evidence that exposure of parents leads to excess heritable disease in offspring(2), but ICRP’s present estimate of genetic risks up to the second generation is 0.2 % per Sv(2), which is small compared with the risk of fatal cancer. RISK COMMUNICATION Radiation is often perceived as something scary – something that is connected with individual descriptions of severe radiation damage after very high radiation doses, nuclear war and reactor accidents such as those in Chernobyl and Fukushima. To balance the often exaggerated fear of radiation among the public with the fact that the radiation in other contexts is neglected requires good knowledge of radiation and radiation protection, and an understanding of the psychology of risk communication. Helpful advice for both the medical field(31 – 33) and for other areas of society(34 – 36) are found in the literature. Risk communication must be based on quality, full transparency and openness, confidence, initiative, swiftness and continuity. The messages must be given in a simple and understandable way, based on the golden rule ‘Never underestimate people’s talents, but do not overestimate their knowledge’ and the communication must be interactive. The information must be clear and understandable for the receiver. Ask people if they understand what you are saying. The best unit to communicate risk-related dose quantities is the mSv. To use more than one unit is confusing. Using mSv, doses from natural background to lethal whole body doses can be reported without the use of decimals(36). Think about how you express yourself and how the information is perceived. Do not give dose information without giving some perspective. A comparison with the yearly dose contributions from natural background radiation is a straightforward way to give
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The other is an Australian study which used a cohort of 10.9 million young people (0 –19 y old). Of 60 674 cancers diagnosed, there were 3150 among those 680 211 persons who had received one or more CT scans, compared with 2542 cancers that would have been expected had there been no effect of CT scans on the cancer risk. This gave 608 extra cancers associated with CT scan exposure for an average follow-up period of almost 10 y(26). These two studies have been criticised(27, 28) for not giving information about indications for the CT investigations and the potential for ‘reverse causation’. i.e. cancers may have been caused by the medical conditions promoting the CT rather than by the absorbed dose from CT. UNSCEAR(28) also concludes that, for about 25 % out of 23 different cancer types (including leukaemia, thyroid, skin, breast and brain cancer), children are clearly more radiosensitive than adults. Still, the absolute risk is very small.
S. MATTSSON AND M. NILSSON
perspective; comparisons with the risk to die from cancer for reasons other than man-made sources of ionising radiation is another(37). The risk of radiationinduced effects is not well understood at the levels of radiation used for most diagnostic procedures. But there are clearly risks associated with not performing an examination that should also be considered. These include missing a diagnosis and/or initiating treatment too late to improve the medical outcome. REFERENCES
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1. ICRP. ICRP statement on tissue reactions/Early and late effects of radiation in normal tissues and organs – Threshold doses for tissue reactions in a radiation protection context. ICRP Publication 118. Ann. ICRP 41(1–2) (2012). 2. ICRP. The 2007 recommendations of the International Commission on Radiological Protection. ICRP Publication 103. Ann. ICRP 37 (2– 4) (2007). 3. Brenner, D. J. et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc. Natl. Acad. Sci. USA 100(24), 13761–13766 (2003). 4. Preston, R. J. et al. Uncertainties in estimating health risks associated with exposure to ionizing radiation. J. Radiol. Prot. 33, 573– 588 (2013). 5. Preston, D. L., Ron, E., Tokuoka, S., Funamoto, S., Nishi, N., Soda, M., Mabuchi, K. and Kodama, K. Solid cancer incidence in atomic bomb survivors: 1958– 1998. Radiat. Res. 168(1), 1– 64 (2007). 6. Kerr, G. D. et al. Workshop report on atomic bomb dosimetry residual radiation exposure: recent research and suggestions for future studies. Health Phys. 105(2), 140– 149 (2013). 7. Boice, J. D. Jr. Ionizing radiation. In: Cancer epidemiology and prevention, Third edn. Schottenfeld, D. and Fraumeni, J. F. Jr, Eds. Oxford University Press, pp. 259– 293 (2006). 8. Radiation Effects Research Foundation. http://www. rerf.jp/general/research_e/index.html. 9. Preston, D. L., Shimizu, Y., Pierce, D. A., Suyamac, A. and Mabuchik, K. Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950–1997. Radiat. Res. 178, 146–172 (2012). 10. Berrington de Gonzalez, A., Gilbert, E., Curtis, R., Inskip, P., Kleinermann, R., Morton, L., Rajaraman, P. and Little, P. Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose–response relationship. Int. J. Radiat. Oncol. Biol. Phys. 86(2), 224–233 (2013). 11. Ron, E. Cancer risks from medical radiation. Health Phys. 85, 47–59 (2003). 12. Lindberg, S. Radiotherapy of childhood haemangiomas: from active treatment to radiation risk estimates. Radiat. Environ. Biophys. 40(3), 179– 189 (2001). 13. Linet, M. S., Slovis, T. L., Miller, D. L., Kleinerman, R., Lee, C., Rajaraman, P. and Berrington de Gonzalez, A. Cancer risks associated with external radiation from diagnostic imaging procedures. CA Cancer J. Clin. 62, 75–100 (2012). 14. Stewart, A. M., Webb, J., Giles, D. and Hewitt, D. Malignant disease in childhood and diagnostic irradiation in utero. Lancet 2(Sept. 1), 447 (1956).
15. Stewart, A., Webb, J. and Hewitt, D. A survey of childhood malignancies. Br. Med. J. 1, 1495–1508, (1958). 16. Knox, E. G., Stewart, A. M., Kneale, G. W. and Gilman, E. A. Prenatal irradiation and childhood cancer. J. Soc. Radiol. Prot. 7, 177– 189 (1987). 17. Doll, R. and Wakeford, R. Risk of childhood cancer from fetal irradiation. Br. J. Radiol. 70, 130 – 139 (1997). 18. Wakeford, R. Radiation in the workplace—a review of studies of the risks of occupational exposure to ionizing radiation. J. Radiol. Prot. 29, A61– A79 (2009). 19. Muirhead, C. R., O’Hagan, J. A., Haylock, R. G., Phillipson, M. A., Willcock, T., Berridge, G. L. C. and Zhang, W. Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers. Br. J. Cancer 100, 206–212 (2009). 20. Cardis, E. et al. The 15-country collaborative study of cancer risk among radiation workers in the nuclear industry: estimates of radiation-related cancer risks. Radiat. Res. 167, 396– 416 (2007). 21. Bhatti, P. et al. Novel breast cancer risk alleles and interaction with ionizing radiation among U.S. radiologic technologists. Radiat. Res. 173, 214– 224 (2010). 22. Shilnikova, N. S. et al. Cancer mortality risk among workers at the Mayak nuclear complex. Radiat. Res. 159(6), 787– 798 (2003). 23. Darby, S. et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case–control studies. BMJ 330, 223–226 (2005). 24. IAEA. Environmental consequences of the Chernobyl accident and their remediation: twenty years of experience. Report of the UN Chernobyl Forum Expert Group “Environment” (EGE), August (2005). 25. Pearce, M. S. et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours; a retrospective cohort study. Lancet 380, 499– 505 (2012). 26. Mathews, J. D. et al. Cancer risk in 680 000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ 346, f2360 (2013). 27. NCRP (National Council on Radiation Protection and Measurements). Uncertainties in the estimation of radiation risks and probability of disease causation. NCRP Report No. 171, Bethesda, MD, USA (2012). 28. UNSCEAR. Sources, Effects and Risks of Ionizing Radiation. Volume II, Scientific Annex B. Effects of Radiation Exposure of Children. United Nations (2013). 29. Brenner, D. J. Extrapolating radiation-induced cancer risks from low doses to very low doses. Health Phys. 97(5), 505– 509 (2009). 30. ICRP. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann. ICRP 21 (1– 3) (1991). 31. Verdun, F. R., Bochud, F., Gudinchet, F., Aroua, A., Schnyder, P. and Meuli, R. Radiation risk: what you should know to tell your patient. Radiographics 28(7), 1807–1816 (2008). 32. Peck, D. J. and Samei, E. How to Understand and Communicate Radiation Risk. http://www.imagewisely. org/Imaging-Professionals/Medical-Physicists/Articles/ How-to-understand-and-communicate-radiation-risk.
CANCER RISKS FROM LOW DOSES OF RADIATION 33. Dauer, L. T., Thornton, R. H., Hay, J. L., Balter, R., Williamson, M. J. and St Germain, J. Fears, feelings, and facts: interactively communicating benefits and risks of medical radiation with patients. Am. J. Roentgenol. 196(4), 756– 761 (2011). 34. Covello, V. T. Risk communication, radiation, and radiological emergencies: strategies, tools, and techniques. Health Phys. 101(5), 511– 530 (2011).
35. Jorgensen, T. J. and Moscovitch, M. Communicating radiation risks to the public. Editorial. Rad. Prot. Dosim. 145(4), 339– 340 (2011). 36. IAEA. Risk communication more than facts and feelings by David Ropeik. IAEA Bulletin 50–1 (2008). 37. Fahey, F. H., Treves, T. and Adelstein, S. J. Minimizing and communicating radiation risk in pediatric nuclear medicine. J. Nucl. Med. 52, 1240– 1251 (2011).
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doi:10.1093/rpd/ncv037
ON THE ESTIMATION OF RADIATION-INDUCED CANCER RISKS FROM VERY LOW DOSES OF RADIATION AND HOW TO COMMUNICATE THESE RISKS So¨ren Mattsson* and Mats Nilsson Medical Radiation Physics, Department of Clinical Sciences Malmo¨, Lund University, Ska˚ne University Hospital Malmo¨, Malmo¨ SE-205 02, Sweden *Corresponding author: [email protected]
INTRODUCTION
CANCER RISK ESTIMATES AT LOW DOSES
It is important to have good knowledge about the effects of low and very low doses (1 – 100 mSv) of radiation in order to make accurate judgements and trade-offs in a number of areas in society. These include the increasing use of diagnostic radiology, particularly computed tomography (CT), screening tests for cancer, positron emission tomography (PET), PET/CT and fluoroscopically guided complex interventions; the future of nuclear energy production and investments in nuclear technology; occupational radiation exposure; risks for flight personnel; remediation of radon and radon daughters and planning to face the consequences of nuclear and radiological accidents and disasters. After low absorbed doses (10 – 100 mSv), no acute harmful tissue effects are seen(1) and for cancer effects, there is a lack of knowledge due to the absence of statistical power as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. For very low absorbed doses (1 – 10 mSv), the possibility to get information from epidemiology is even more limited(2 – 4). The aim of this article is to review the current knowledge on cancer risks from low and very low absorbed doses (1 – 100 mSv) of ionising radiation and to discuss ways to inform about these risks.
Survivors from Hiroshima and Nagasaki—The Life Span Study cohort, Japan The most informative set of data on the effects of whole body exposures of high-dose-rate gamma radiation (with a small contribution from neutrons) comes from studies of the over 100 000 survivors (including 30 000 children) of the detonations of nuclear weapons over the cities of Hiroshima and Nagasaki in Japan in 1945, the so-called Life Span Study (LSS). The advantages of the LSS are the wide dose range, wide range in age at exposure and long-term followup(2, 5 – 8). The LSS is often described as a high-dose study, but the mean dose in the exposed LSS cohort is only 200 mSv ranging from 5 mSv to 2 –4 Sv. More than half of the exposed individuals received doses ,50 mSv(3, 5). In the latest LSS cohort mortality report (9), there is no indication that the slope of the dose –response curve for solid cancers over the low-dose range restricted to survivors with dose estimates lower than 120 mSv differs significantly from that for the full range and there was no evidence for a threshold. Minimum latency periods of 2– 5 y were apparent for leukaemia (except for chronic lymphocytic leukaemia), but were longer for solid tumours. Excess risk persisted throughout life for most malignancies. For
# The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://rpd.oxfordjournals.org/ at Seton Hall on April 1, 2015
The article is intended to give a short overview of epidemiological data on cancer risks associated with very low absorbed doses of ionising radiation. The linear no-threshold (LNT) approach to estimate cancer risks involves the use of epidemiological data at higher doses (>100 mSv), but is supported by data from lower exposure of more sensitive population groups like fetuses and children and the presence of rare types of cancer. The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with a dose and dose-rate effectiveness (reduction) factor (DDREF) of 2 for extrapolation from high doses, should be used. The numerical value of the DDREF is challenged by the findings from some recent epidemiological studies demonstrating risks per unit dose compatible with the risks observed in the higher dose studies. In general there is very limited knowledge about the cancer risk after low absorbed doses (10 –100 mSv), as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. Even if there may be significant deviations from linearity in the relevant dose range 0– 100 mSv, one does not know the magnitude or even the direction of any such deviations. The risks could be lower than those predicted by a linear extrapolation, but they could also be higher. Until more results concerning the effects of low-dose exposure are available, a reasonable radiation protection approach is to consider the risk proportional to the dose.
S. MATTSSON AND M. NILSSON
cancer incidence (and cancer mortality), the dose– response relationship may be described in various ways; by a linear or a curvilinear function. The results also show substantial differences in the risk of cancer for various organs/tissues. A detailed fit of the dose– response curve to the experimental points shows a fine structure which indicates a greater complexity than described by a linear or simple curvilinear function. Patients having received radiation therapy or multiple X-ray examinations
Studies of in utero X rays and cancer risks in offspring In utero diagnostic X rays (mainly pelvimetry) were linked to an excess of paediatric cancer mortality in offspring as first reported by Stewart et al.(14, 15) already in 1956 and later confirmed(16). In 1997 Doll and Wakeford(17) concluded that irradiation of the fetus in utero increases the risk of childhood cancer with about 6 % per Sv at doses of the order of 10 mSv.
Environmental exposures (radon and radon daughters in houses and workplace, Chernobyl fallout, etc.) Radon, particularly in combination with smoking, constitutes an important public health risk(23). In a collaborative analysis of data from 13 European case– control studies it was concluded that the increase in lung cancer was 16 % (5–31 %) per 100 Bq m23 increase in radon concentration. The dose–response relation seemed to be linear with no threshold and remained significant ( p ¼ 0.04) in analyses limited to individuals from homes with measured radon concentration ,200 Bq m23. In the absence of other causes of death, the absolute risks of lung cancer by age 75 y at usual radon concentrations of 0, 100 and 400 Bq m23 would be 0.4, 0.5 and 0.7 %, respectively, for lifelong non-smokers, and about 25 times greater (10, 12 and 16 %) for cigarette smokers(23). After Chernobyl and among the residents of Belarus, Russia and Ukraine more than 6000 cases (up to the year 2005) of thyroid cancer have been reported in those who were internally exposed to radioactive iodine as children and adolescents at the time of the accident, and more cases can be expected(24).
Occupationally exposed persons These groups include medical staff (radiographers and radiologists), aircraft crews, radium workers, especially instrument dial painters, miners, Chernobyl accident emergency and recovery workers, participants in nuclear weapons tests, and workers in the nuclear weapons and power industries(18). Underground miners have generated estimates of lung cancer risk from radon and its daughters. Radium dial painters have shown a clear
Risk from paediatric CT There are two recent publications. One is a follow-up study of 180 000 young people (0–21 y old) who had CT scans in the UK during 1985–2002. It shows an increase in risks of leukaemia and brain cancer with an increase in doses of radiation from a previous CT scan and gave provisional risk estimates for these two cancers(25).
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Secondary cancers that develop after radiation therapy for cancer(10) and in earlier days also for benign conditions(11) mainly affect the part of the body that was treated. In general, the lifetime risk of a secondary cancer is highest in people treated for cancer as children or adolescents. The dose–response patterns for cancer risks associated with high-dose fractionated radiotherapy are generally similar to those of the atomic bomb survivors, but the risk per Sv is lower for patients treated with high-dose fractionated external radiotherapy compared with that for atomic bomb survivors, likely due to a higher degree of cell killing in the patient group(10). Follow-up of individuals treated as children (0–1.5 y) for childhood skin haemangiomas with low-dose radiotherapy has shown significantly increased numbers of tumours in the central nervous system, thyroid and other endocrine glands (pituitary and parathyroid glands), and breast(12). In studies of patients having undergone repeated fluoroscopic imaging examinations for tuberculosis, there is a significant dose–response association with breast cancer, but not with lung cancer(13). There are also limited data suggesting a possible risk of chronic myeloid leukaemia.
excess of bone cancer arising from large intake of radium. Nuclear workers have experienced radiation dose-related incidence and mortality risk increases for leukaemia (excluding chronic lymphocytic leukaemia). In the UK, incidence was slightly more elevated (ERR per Sv, 1.7; 90 % CI, 0.06–4.3) than the dose-associated risks of the atomic bomb survivors (ERR per Sv, 1.4; 90 % CI, 0.1–3.4)(19). These workers also had statistically significant increases for all cancers combined other than leukaemia. Dose-associated increases were also apparent for lung cancer in a 15-country study, although the associations with lung cancer may have been confounded by smoking(20). Recently, a statistical association was reported between chromosome translocation frequencies in cultures of peripheral blood lymphocytes and increasing radiation dose score based on numbers and types of diagnostic X-ray examinations in a cohort of US radiological technologists(21). Valuable information on significant long-term effects from low-dose exposures to internally incorporated radionuclides has been provided by epidemiological studies of the health of workers from the Mayak nuclear complex in the Southern Urals of Russia(22).
CANCER RISKS FROM LOW DOSES OF RADIATION
Biophysical argument for linearity The possible cancer risks caused by ionising radiation doses of 100 mSv or less are too small to be estimated directly from epidemiological data involving all age groups and all cancers even in a large population group. The linear no-threshold (LNT) approach to estimate such risks involves the use of epidemiological data at higher doses, but is supported by data from exposure of more sensitive groups like fetuses and children and the presence of rare types of cancer, establishing an ‘anchor point’ for the linear model, around 6 –10 mSv(29). For the type of X rays used, 6 –10 mSv means an average of around one-hit per cell. Based on the single-cell hit theory, it is therefore likely that half the dose gives half the risk and so on. At lower doses than 6–10 mSv these arguments speak for linearity down to very low doses(29). Summary of cancer risk estimates at low doses The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with an uncertain dose and dose-rate effectiveness (reduction) factor (DDREF) of two for extrapolation from high doses, is a prudent basis for radiation protection at low doses and low dose rates. The numerical value of the DDREF is challenged by the findings from recent epidemiological studies demonstrating risks compatible with the risks observed in the higher dose studies(2). There is evidence that a small risk of cancer results from low-level exposure to radiation and that the excess risk is around that predicted by current risk models (Table 1). More open is an issue how different cancer types respond to radiation. Because the results of human epidemiology studies as well as radiation effects on animals and cell
Table 1. Nominal probability coefficients for cancer after exposure to radiation at low dose and dose rate. Probability of fatal cancer, % per Sv Year of the estimate Entire population Adults only
1990(30) 7.3 5.6
2007(2) 5.7 4.2
In Publ 103(2) the estimate is based on cancer incidence weighted for lethality and life impairment, whereas in Publ 60(30) the estimate is based on fatal cancer risk weighted for non-fatal cancer, relative life lost for fatal cancers and life impairment for non-fatal cancer.
cultures may be interpreted differently, variations in published relative risk values are seen. ICRP and many other authors use an average value of 5 % per Sv as an approximated overall detriment coefficient. There continues to be no direct evidence that exposure of parents leads to excess heritable disease in offspring(2), but ICRP’s present estimate of genetic risks up to the second generation is 0.2 % per Sv(2), which is small compared with the risk of fatal cancer. RISK COMMUNICATION Radiation is often perceived as something scary – something that is connected with individual descriptions of severe radiation damage after very high radiation doses, nuclear war and reactor accidents such as those in Chernobyl and Fukushima. To balance the often exaggerated fear of radiation among the public with the fact that the radiation in other contexts is neglected requires good knowledge of radiation and radiation protection, and an understanding of the psychology of risk communication. Helpful advice for both the medical field(31 – 33) and for other areas of society(34 – 36) are found in the literature. Risk communication must be based on quality, full transparency and openness, confidence, initiative, swiftness and continuity. The messages must be given in a simple and understandable way, based on the golden rule ‘Never underestimate people’s talents, but do not overestimate their knowledge’ and the communication must be interactive. The information must be clear and understandable for the receiver. Ask people if they understand what you are saying. The best unit to communicate risk-related dose quantities is the mSv. To use more than one unit is confusing. Using mSv, doses from natural background to lethal whole body doses can be reported without the use of decimals(36). Think about how you express yourself and how the information is perceived. Do not give dose information without giving some perspective. A comparison with the yearly dose contributions from natural background radiation is a straightforward way to give
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The other is an Australian study which used a cohort of 10.9 million young people (0 –19 y old). Of 60 674 cancers diagnosed, there were 3150 among those 680 211 persons who had received one or more CT scans, compared with 2542 cancers that would have been expected had there been no effect of CT scans on the cancer risk. This gave 608 extra cancers associated with CT scan exposure for an average follow-up period of almost 10 y(26). These two studies have been criticised(27, 28) for not giving information about indications for the CT investigations and the potential for ‘reverse causation’. i.e. cancers may have been caused by the medical conditions promoting the CT rather than by the absorbed dose from CT. UNSCEAR(28) also concludes that, for about 25 % out of 23 different cancer types (including leukaemia, thyroid, skin, breast and brain cancer), children are clearly more radiosensitive than adults. Still, the absolute risk is very small.
S. MATTSSON AND M. NILSSON
perspective; comparisons with the risk to die from cancer for reasons other than man-made sources of ionising radiation is another(37). The risk of radiationinduced effects is not well understood at the levels of radiation used for most diagnostic procedures. But there are clearly risks associated with not performing an examination that should also be considered. These include missing a diagnosis and/or initiating treatment too late to improve the medical outcome. REFERENCES
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15. Stewart, A., Webb, J. and Hewitt, D. A survey of childhood malignancies. Br. Med. J. 1, 1495–1508, (1958). 16. Knox, E. G., Stewart, A. M., Kneale, G. W. and Gilman, E. A. Prenatal irradiation and childhood cancer. J. Soc. Radiol. Prot. 7, 177– 189 (1987). 17. Doll, R. and Wakeford, R. Risk of childhood cancer from fetal irradiation. Br. J. Radiol. 70, 130 – 139 (1997). 18. Wakeford, R. Radiation in the workplace—a review of studies of the risks of occupational exposure to ionizing radiation. J. Radiol. Prot. 29, A61– A79 (2009). 19. Muirhead, C. R., O’Hagan, J. A., Haylock, R. G., Phillipson, M. A., Willcock, T., Berridge, G. L. C. and Zhang, W. Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers. Br. J. Cancer 100, 206–212 (2009). 20. Cardis, E. et al. The 15-country collaborative study of cancer risk among radiation workers in the nuclear industry: estimates of radiation-related cancer risks. Radiat. Res. 167, 396– 416 (2007). 21. Bhatti, P. et al. Novel breast cancer risk alleles and interaction with ionizing radiation among U.S. radiologic technologists. Radiat. Res. 173, 214– 224 (2010). 22. Shilnikova, N. S. et al. Cancer mortality risk among workers at the Mayak nuclear complex. Radiat. Res. 159(6), 787– 798 (2003). 23. Darby, S. et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case–control studies. BMJ 330, 223–226 (2005). 24. IAEA. Environmental consequences of the Chernobyl accident and their remediation: twenty years of experience. Report of the UN Chernobyl Forum Expert Group “Environment” (EGE), August (2005). 25. Pearce, M. S. et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours; a retrospective cohort study. Lancet 380, 499– 505 (2012). 26. Mathews, J. D. et al. Cancer risk in 680 000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ 346, f2360 (2013). 27. NCRP (National Council on Radiation Protection and Measurements). Uncertainties in the estimation of radiation risks and probability of disease causation. NCRP Report No. 171, Bethesda, MD, USA (2012). 28. UNSCEAR. Sources, Effects and Risks of Ionizing Radiation. Volume II, Scientific Annex B. Effects of Radiation Exposure of Children. United Nations (2013). 29. Brenner, D. J. Extrapolating radiation-induced cancer risks from low doses to very low doses. Health Phys. 97(5), 505– 509 (2009). 30. ICRP. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann. ICRP 21 (1– 3) (1991). 31. Verdun, F. R., Bochud, F., Gudinchet, F., Aroua, A., Schnyder, P. and Meuli, R. Radiation risk: what you should know to tell your patient. Radiographics 28(7), 1807–1816 (2008). 32. Peck, D. J. and Samei, E. How to Understand and Communicate Radiation Risk. http://www.imagewisely. org/Imaging-Professionals/Medical-Physicists/Articles/ How-to-understand-and-communicate-radiation-risk.
CANCER RISKS FROM LOW DOSES OF RADIATION 33. Dauer, L. T., Thornton, R. H., Hay, J. L., Balter, R., Williamson, M. J. and St Germain, J. Fears, feelings, and facts: interactively communicating benefits and risks of medical radiation with patients. Am. J. Roentgenol. 196(4), 756– 761 (2011). 34. Covello, V. T. Risk communication, radiation, and radiological emergencies: strategies, tools, and techniques. Health Phys. 101(5), 511– 530 (2011).
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