IJE Advance Access published online on July 9, 2008
International Journal of Epidemiology, doi:10.1093/ije/dyn123
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Comments on the study of McGeoghegan et al.
Westlakes Scientific Consulting, Westlakes Science Park, Moor Row, Cumbria CA24 3LN.
*Corresponding author. Westlakes Scientific Consulting, Westlakes Science Park, Moor Row, Cumbria CA24 3LN. E-mail: steve.jones{at}westlakes.ac.uk
We agree with Little, Tawn, Tzoulaki et al.1 that the findings of our recent study of male workers at British Nuclear Fuels plc2 should be treated with caution in respect of any causal interpretation, and hope that this was clear to readers of our article.
We also agree with the comments of Little, Tawn, Tzoulaki et al. that studies of radiotherapy patients3, whilst important in their own right, are unlikely to assist with the question of whether chronic occupational exposure to ionizing radiation can cause increased risks of circulatory disease (or other non-cancer diseases), as operation of common biological mechanisms in these two very different exposure regimes cannot reliably be inferred.
However, we point out that the results of the meta-analysis reported by Little, Tawn, Tzoulaki et al. must also be treated with a degree of caution. The strength of evidence provided by an individual study depends on a number of factors, including the study size, the range of exposures studied, the reliability and detail of the exposure information used in the analysis and the length of follow-up of the subjects. A particular case in point is the study of workers at the Mayak complex by Bolotnikova, Koshurnikova, Komleva et al.4 This study is little more than exploratory, reporting raw and age standardized rates of mortality from cardiovascular disease of male workers in three groups—those not subject to specific control of exposure to radiation, those with cumulative exposures <1 Gy, and those with cumulative exposure 
1 Gy. There is no adjustment for socioeconomic status. Bolotnikova, Koshurnikova, Komleva et al. do not report any estimates of the coefficient of excess relative risk from their data; this is derived in the earlier review article by Little, Tawn, Tzoulaki et al.5 However, the confidence intervals resulting from this calculation attach considerable weight to the result derived from the Bolotnikova, Koshurnikova, Komleva et al. study, such that it is highly influential in the meta-analysis of all 11 studies considered by Little, Tawn, Tzoulaki et al. (1/
i2 
1.1 x 103, compared with 
[1/i2] 3.6 x 103 for all studies), and completely dominant in the analysis of the six environmental and occupational studies (1/i2 1.1 x 103, compared with [1/i2] 1.2 x 103 for all environmental and occupational studies). As a result, on this formalism it would require a substantial amount of additional positive evidence from large and well controlled occupational studies to alter a conclusion driven by a single relatively small and exploratory study.
As noted by Little, Tawn, Tzoulaki et al., at present a cause-and-effect interpretation of the reported statistical associations between occupational exposure to ionizing radiation and circulatory disease cannot be reliably inferred, but neither can it be reliably excluded. Further high quality occupational studies, with long follow up and better control of confounding, will be of assistance; greater understanding of the mechanisms by which chronic low-dose exposure to ionizing radiation may, or may not, increase the risk of circulatory disease would be especially informative.
In memory of Dave McGeoghegan, who died suddenly and unexpectedly on 26 May 2008. He will be greatly missed by his family and friends, and by his colleagues throughout the epidemiological community.
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1 Little MP, Tawn EJ, Tzoulaki I, et al. Comments of the study of McGeoghegan et al. Int J Epidemiol (2008) (in press).
2 McGeoghegan D, Binks K, Gillies M, Jones S, Whaley S. The non-cancer mortality experience of male workers at British Nuclear Fuels plc, 1946-2005. Int J Epidemiol (2008) 37:506-a–18.
3 McGale P, Darby S. Commentary: A dose-response relationship for radiation-induced heart disease – current issues and future prospects. Int J Epidemiol (2008) 37:518–23.
4 Bolotnikova MG, Koshurnikova NA, Komleva EB, Budushchev EB, Okatenko PV. Mortality from cardiovascular diseases among male workers at the radiochemical plant of the ‘Mayak’ complex. Sci Total Environ (1994) 142:29–31.[CrossRef][Medline]
5 Little MP, Tawn EJ, Tzoulaki I, et al. A systematic review of epidemiological associations between low and moderate doses of ionizing radiation and late cardiovascular effects, and their possible mechanisms. Radiat Res (2008) 169:99–109.[CrossRef][Web of Science][Medline]
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