Introduction: In this study, the authors conducted a comprehensive systematic review and meta-analysis (including a dose-response meta-analysis) for a possible causal association between residential radon exposure and leukemia. All 3 types of study design, including ecological, case-control, and cohort studies, were included in this study. In particular, different measurement units of radon exposure among studies were dealt with and analyzed thoroughly.
Methods: A medical librarian searched MEDLINE (PubMed), EMBASE, and the Cochrane Library (from January 01, 1970 to November 05, 2020). For ecological studies, a conventional meta-analysis and subgroup analyses with meta-ANOVA analyses were conducted. For case-control and cohort studies, a two-stage dose-response meta-analysis was conducted.
Results: A total of 8 ecological, 9 case-control, and 15 ecological-cohort studies were analyzed. For ecological studies, the pooled correlation coefficient was 0.48 (95% CI 0.41-0.54). In the meta-analysis of variance (ANOVA) analyses, the age group (childhood vs. adult) showed a statistically significant result (Q = 7.93 and p = 0.019) with the pooled correlation coefficient for childhood, adult, and all age group of 0.67 (95% CI 0.53-0.77), 0.46 (95% CI 0.05-0.74), and 0.44 (95% CI 0.36-0.51), respectively. For case-control studies, the dose-response meta-analysis showed the pooled OR increase of 1.0308 (95% CI 1.0050-1.0573) for each 100 Bq/m3 increase of radon dose. The pooled OR increase was 1.0361 (95% CI 1.0014-1.0720) for each 100 Bq/m3 increase of radon dose for lymphoid leukemia subgroup and 1.0309 (95% CI 1.0050-1.0575) for each 100 Bq/m3 increase of radon dose for childhood leukemia subgroup. Because of the inclusion of ecological studies with larger exposure assessment units, the pooled RR from ecological-cohort studies should be interpreted conservatively (a tendency towards a higher risk estimate). The overall pooled RR increase for each 100 Bq/m3 increase of radon dose was 1.1221 (95% CI 1.0184-1.2363). The pooled RR increase was 1.2257 (95% CI 1.0034-1.4972) for each 100 Bq/m3 increase of radon dose for the myeloid leukemia subgroup and 1.2503 (95% CI 1.0233-1.5276) for each 100 Bq/m3 increase of radon dose for adult leukemia subgroup.
Discussion: A number of epidemiologic concepts, including the issue of sample size justification, the possibility of differential participation selection bias for case-control studies, the possibility of random and systematic errors in radon measurement, ecological fallacy for ecological studies, were discussed. The effect of age group, socioeconomic status, and gamma radiation exposure was also discussed. Future more accurate and conclusive large-scale case-control and cohort studies are needed.
Keywords: Dose-response meta-analysis; Leukemia; Meta-analysis; Meta-analysis-of-variance method; Residential radon.
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