A meta-analysis of leukaemia risk from protracted exposure to low-dose gamma radiation

Abstract

Context: More than 400,000 workers annually receive a measurable radiation dose and may be at increased risk of radiation-induced leukaemia. It is unclear whether leukaemia risk is elevated with protracted, low-dose exposure.

Objective: We conducted a meta-analysis examining the relationship between protracted low-dose ionising radiation exposure and leukaemia.

Data sources: Reviews by the National Academies and United Nations provided a summary of informative studies published before 2005. PubMed and Embase databases were searched for additional occupational and environmental studies published between 2005 and 2009.

Study selection: We selected 23 studies that: (1) examined the association between protracted exposures to ionising radiation and leukaemia excluding chronic lymphocytic subtype; (2) were a cohort or nested case-control design without major bias; (3) reported quantitative estimates of exposure; and (4) conducted exposure-response analyses using relative or excess RR per unit exposure.

Methods: Studies were further screened to reduce information overlap. Random effects models were developed to summarise between-study variance and obtain an aggregate estimate of the excess RR at 100 mGy. Publication bias was assessed by trim and fill and Rosenthal's file drawer methods.

Results: We found an ERR at 100 mGy of 0.19 (95% CI 0.07 to 0.32) by modelling results from 10 studies and adjusting for publication bias. Between-study variance was not evident (p=0.99).

Conclusions: Protracted exposure to low-dose gamma radiation is significantly associated with leukaemia. Our estimate agreed well with the leukaemia risk observed among exposed adults in the Life Span Study (LSS) of atomic bomb survivors, providing increased confidence in the current understanding of leukaemia risk from ionising radiation. However, unlike the estimates obtained from the LSS, our model provides a precise, quantitative summary of the direct estimates of excess risk from studies of protracted radiation exposures.

Figure 1

Forest plots of model I (top) and model II (bottom) random effects models estimating RR at 100 mGy. Dotted line references no effect (ie, RR=1). The effect point sizes (■) are drawn proportional to the inverse of the sampling variances. Lower bound of confidence intervals may differ from published values because of assumptions on standard errors.

Figure 2

Funnel plots for model I (panel A) and model II (panel B) showing the effect size versus standard error (log scale). Plot also shows the results' trim and fill analyses, that is, the actual studies (filled circles), the missing studies (open circles) and the 95% CI (dotted lines).