We observed a statistically significant increase in translocation frequency (p = 0.001) with increasing cumulative diagnostic RBM radiation dose score after adjusting for age. The estimate for the slope was unchanged and independent of radiation dose from occupational exposures, as evidenced by multivariate analysis that included several potential confounding variables. We are among the first to show that accumulated radiation doses from a lifetime of routine x-ray examinations was statistically significantly associated with increased cytogenetic damage in the form of chromosome translocations. Extreme values do not explain our finding because the association remained robust after excluding outliers.
Our ability to detect a low-dose relationship, despite the older ages of the radiologic technologists, their relatively low cumulative personal diagnostic RBM radiation dose scores, and the substantial inter-individual variability in translocation frequencies, was enhanced by study features designed to overcome these limitations (11
). The features were the very large sample size, the scoring of 1828 cells on average (1024 cell equivalents) per person (274,234 cells in the whole study), and the ability to select participants who were homogeneous for age. Additionally, we tried to reduce the effect of cigarette smoking on translocation frequencies by restricting the selected sample to non- or ex-smokers. While previous studies examining the influence of cigarette smoking on translocation frequency have not been consistent (13
), a recent pooled study demonstrated a significant increased frequency of chromosome translocations associated with ever smoking (40
An alternative explanation for why we detected a low-dose relationship may be that we did not lower the limits of detection, but rather the radiation doses were in fact higher because the radiologic technologists under-reported x-ray examinations (41
) or repeated x-rays were performed when images were of low quality. Our analysis of the reproducibility of self-reporting among 354 technologists who completed the same questionnaire twice within a four year period showed an overall 80% agreement, suggesting radiologic technologists are consistent in their recall of the number of past diagnostic procedures (78% agreement) and the time period they first occurred (83% agreement).
The cytogenetic damage we detected appeared to be associated with more recent routine x-ray examinations because 72% of the collective cumulative medical RBM radiation dose scores occurred after 1969. This is of concern because of the large increase in medical radiation exposure since 19891
and because increased frequencies of chromosome aberrations have been associated with elevated cancer risk (reviewed in 8). While the link between radiation exposure from personal diagnostic procedures, chromosome aberrations, and cancer risk is indirect, ionizing radiation is a well known carcinogen.
In studies of high energy gamma rays, the expected frequency of excess translocations per 100 CEs per 1 mGy is 0.0015 (43
). The distribution of applicable photon energies in the present study were x-rays of approximately 100 keV or less. For dicentrics, the unstable counterpart of translocations, the linear term for x-rays of 50–100 keV is about two to three times higher than that for high energy gamma-rays (44
). So, for the relevant energies here, an estimated frequency of 0.005 excess translocations/100 CE/mGy is reasonable. If one exposure score unit approximates 1 mGy, the observed association of 0.004 excess translocations/100 CEs/unit diagnostic RBM radiation dose score (95% CI, 0.002–0.007) was consistent with this estimate and generally similar to the occupational RBM estimate of 0.009 excess translocations/100 CE/mGy (95% CI -0.001–0.02, p = 0.07) in the same group of technologists (21
). Among the 79 technologists for whom FISH analysis was done over a decade earlier, we estimated 0.007 translocations per 100 CEs per score unit (95% CI, 0.002 to 0.013; P=0.01, (22
)). Lending further support to our findings are estimates from Hiroshima and Nagasaki atomic bomb survivors in which the proportion of cells with at least one stable aberration, a similar measure considering the generally low frequencies of translocations, increased by about 0.007/100 CE/mGy and 0.004/100 CE/mGy RBM absorbed dose, respectively (17
). Acknowledging the dosimetric uncertainties in both studies, similar estimates might be expected because the effect of exposure to higher energy gamma rays in the atomic bomb survivors (45
) could be counterbalanced by the protracted radiation exposure in the radiologic technologists.
Recall error of past diagnostic x-ray procedures has been a legitimate obstacle for conducting large population-based health outcome studies relying on self-report (2
). However, because the technologists did not know their translocation frequencies, any recall error would be non-differential with respect to the outcome measure and would probably attenuate relationships observed, not create them. We lacked information on environmental toxins that could be related to increased chromosome translocations, however these unmeasured variables would also need to be related to medical x-ray examinations to confound the relationship we observed. Given the absence of confounding for several candidate variables we measured and analyzed, the masking of a true association with an unmeasured co-variate is unlikely.
This is one of the first studies to report a significant association between chromosome translocations and estimated cumulative diagnostic RBM radiation exposure. We found that radiation from routine x-ray examinations among radiologic technologists was associated with increased chromosome damage, which has been related to elevated cancer risk. Further, the magnitude of the relationship was consistent with expectation based on knowledge of radiation quality and cytogenetic experience. In an earlier study, we found similar results based on 79 radiologic technologists from the same cohort for whom432 whole genome equivalents per person were analyzed (22
). The present work, which was done in a different laboratory, improves on the first study by increasing the sample size and the number of cells examined per person. While disease diagnosis and patient treatment have been markedly improved by medical uses of radiation, the dose to the individual from diagnostic tests should be monitored and reduced when possible. Our data indicate the need for careful evaluation before recommending diagnostic radiologic examinations, especially in light of the recent and substantial proliferation in the US of high-dose examinations, including CT and nuclear medicine procedures. For example, incidental findings of uncertain clinical significance on CTs are followed by additional scans that may not result in patient benefit. Dose reduction can be achieved without lowering diagnostic accuracy1
, making judicious choices by understanding effective doses from each of the various procedures (4
), oversight of cumulative patient doses, and the avoidance of repeats of poor initial quality diagnostic x-ray examinations.