Low Radiation Doses: Small Risks? No Risks? Or Risks to Only a Few?

See also the article by Sakane et al in this issue.

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Whereas the benefits of CT in almost every sphere of medicine are indisputable, over the last 2 decades the potential cancer risks associated with low doses of radiation from CT have been much discussed and debated. Undoubtedly doses from one or two CT examinations carry smaller risk for cancer than higher radiation doses, but is the risk actually zero? More than 90 million CT examinations are performed each year in the United States and so the sheer numbers of individuals exposed makes this a pertinent question.

A number of different approaches have been used to estimate possible cancer risks associated with the low doses of radiation from CT examinations. The modelers were first, estimating CT cancer risks on the basis of survivors of the atomic bomb who were exposed to low radiation doses (1). Next, epidemiologists performed direct studies of cancer risks in individuals who underwent CT as children (2,3). Results from these two approaches are in broad agreement (4), suggesting small but nonzero risks. Both approaches have some methodologic issues, which is not surprising when the estimated risks are so much smaller than background cancer risks. In such situations, biases are inevitable, and the significance of these biases needs to be carefully assessed (5).

In this issue, Sakane et al (6) have taken a third approach to the problem. They measured DNA double-strand breaks and unstable chromosome aberrations in the blood of over 100 individuals who underwent standard-dose chest CT examinations (5-mSv effective dose, 13.3-mGy blood dose) and over 100 individuals who underwent low-dose chest CT examinations (1.5-mSv effective dose, 3.5-mGy blood dose). Measurements were taken both before and after the examination. Although not a new approach, it represents a substantial advance because of the scale of the study, its use of two doses, and two DNA damage end points.

For both dose groups, the authors observed increased DNA damage after the CT examination versus before the examination. However, whereas the increased DNA damage was statistically significant in the standard CT dose group, the increase in the low CT dose group was smaller and no longer significant. This pattern reflects low-dose radiation epidemiologic studies of cancer risk, in which as the dose and the risk decrease, exponentially more participants are required in the study to achieve statistical significance (7). Sakane and colleagues (6), however, studied approximately the same number of individuals in both dose groups, so loss of statistical significance at the lower dose is not surprising.

Another way of looking at these results is in terms of the numbers of individuals affected: 64% of the participants in the standard-dose CT group showed increased DNA double-strand breaks, whereas among participants in the low-dose CT group (in whom the dose was decreased almost four-fold) about 47% still showed increased DNA damage. So, even with a substantially reduced dose, the number of affected individuals changed comparatively little. This hint of a radiosensitive subpopulation dominating the risk is reminiscent of the groundbreaking study (8) of North African families who emigrated to Israel and underwent low-dose scalp irradiation for tinea capitis. That study strongly suggested that sensitivity to low-dose radiation–induced meningioma was highly familial and thus also largely limited to a radiosensitive subpopulation.

Sakane et al (6) are conservative regarding the implication of their DNA damage results, although they do reference one epidemiologic study suggesting a potential link between DNA double-strand breaks and cancer risk; however taking all the available evidence to date, it would be fair to say that such a causal link is not well established at this time (9). If such a link did indeed exist, then the results from this study would of course imply that we should optimize or reduce CT doses per examination as much as is practically possible, which is a conclusion that few would debate. A second conclusion, again not unfamiliar, is that whereas the study is admirably large, it is not large enough at the lower dose to provide good evidence either way regarding “zero risk.” But because most CT examinations represent an enormous benefit to the patient, whether the radiation risk is zero or just very small is neither here nor there for a patient who needs to undergo CT. It is, however, relevant for the 20% (or possibly 10% or 30%) of patients who undergo CT without a good clinical rationale (10). For these patients, the benefit-risk balance is different and must be much smaller.

Finally, there are hints in these results (6) that support earlier studies (8) suggesting that perhaps we should not be thinking of the general population as having a single bell-shaped distribution of radiosensitivities. It may be better described as two distinct populations, the larger one less sensitive to low radiation doses and the smaller one much more sensitive. If only we could identify the individuals in each group!

Disclosures of Conflicts of Interest: D.J.B. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed money paid to author for board membership from F3 Platform Biologics. Other relationships: disclosed no relevant relationships.