Table 3.
Direct and indirect assessments of confounding reported in studies of leukemia*
| Relevant study no. | Relevant study name (reference) | Confounder(s) considered | Outcome(s) for confounding | Effect of adjustment on ERR | Comment | Reference for confounding |
|---|---|---|---|---|---|---|
| Environmental studies | ||||||
| 1 | Chornobyl residents (19) | SES | Leukemia | Not reported | Generally similar education level of parents (as a proxy for SES) for cases and controls | Davis et al. 2006 (19) |
| 4 | GB background (26) | SES (Carstair's deprivation index based on census ward and father’s occupation) | Childhood leukemia | −32% to +32%, depending on SES metric |
Main risk estimate adjusted for SES. May be relevant for similar studies |
Kendall et al. 2013b (65) |
| Radon | Childhood leukemia | −42% | A model including both gamma and radon dose to red bone marrow showed reduced ERR/Sv compared with model with just gamma dose | Kendall et al. 2013a (26) | ||
| 3 | China background (23) | Diet and nutrition, drinking water, pesticide residue, and Aflatoxin B1 in food, medical exposures, tobacco smoking, alcohol consumption | Leukemia | Not reported | Distributions of those potential confounding factors did not differ much between high background radiation and control areas | Tao et al. 2012 (23); Tao et al. 1996 (48); Zha et al. 1997 (49) |
| 5 | Swiss background (25) | Residential mobility | Childhood leukemia | +28% when restricting to children with stable residence | Main risk estimate is not adjusted for residence | Spycher et al. 2015 (25) |
| Radon | Childhood leukemia | Not reported | In a separate study, radon exposure not associated with childhood leukemia (HR at 90% radon percentile = 0.93, 95% CI = 0.74 to 1.16, compared with median radon) | Hauri et al. 2013 (50) | ||
| 7 | Finnish background (24) | Down syndrome, birth weight (large for gestational age), maternal smoking, CT | Leukemia and leukemia subtypes | Not reported | Little change when accounting for these factors | Nikkila et al. 2016 (24) |
| Medical studies | ||||||
| 10,11 (11 adjusted for SES) | French & UK pediatric CT (28, 29) | SES | Leukemia | Not reported | Lower frequency of CT scans among higher SES groups; leukemia incidence appears somewhat higher among children from households with higher SES (ie, SES confounding would attenuate ERR) | Pearce et al. 2012 (66); Meulepas et al. 2017 (67) |
| SES | Leukemia | <2% | RRs for dose categories differed by <2% when adjusted for quintiles of household income per postal area (average population, 40 persons) | Meulepas et al. 2019 (52) | ||
| CSS | Leukemia | None | Radiation risks unlikely substantially confounded by CSS | Meulepas et al. 2016 (53) | ||
| 10 | French pediatric CT (28) | CSS | Leukemia | −18% | Adjustment for presence of any leukemia-specific CSS (mean cumulative bone marrow dose = 8.8 mGy and 10.4 mGy among children with and without leukemia-specific CSS). HR per bone marrow dose did not change when children with leukemia-specific CSS were excluded | Journy et al. 2016a (28); Journy et al. 2016b (54) |
| 11 | UK pediatric CT (29) | CSS | Leukemia | None | Exclusion of patients with CSS did not alter dose–response relationship | Berrington et al. 2016 (29) |
| Previous unreported cancers | Leukemia | −15% | Based on confounder data for 40% of cohort | Berrington et al. 2016 (29) | ||
| Occupational studies | ||||||
| 14 | Chornobyl liquidators: Belarus, Russia, & Baltic countries (32) | Education, smoking, alcohol use, occupational and medical history, organization that sent liquidator to Chornobyl, date of start of mission, duration of mission, work on industrial site, personal monitoring of dose, use of protective measures, marital status | Leukemia/lymphoma incidence | Not reported | Authors state that none of these factors modified OR by 10% or more | Kesmeniene et al. 2012 (68) |
| 20 | Chornobyl liquidators: Ukraine (38) | Education, smoking, alcohol use, medical or diagnostic radiation exposures, occupational exposures to chemicals or radiation before and after Chornobyl accident, urban/rural residential status at interview, age and year of first clean-up mission, type of work, total number of missions | Leukemia incidence | Not reported | Authors state that distribution of these factors did not significantly differ between cases and controls | Zablotska et al. 2013 (38) |
| 17 | Rocketdyne nuclear workers (35) | Internal radiation | Leukemia | Not reported | Authors state “other than for lung dose and bone marrow dose, the contribution of internal radiation dose to organs or tissues was not appreciable” | Boice et al. 2011 (35) |
| 22,23 | US nuclear workers/ INWORKS (40, 41) | Benzene; cigarette smoking; plutonium dose | Leukemia | −16% to −41%; −9%; +4% | Benzene confounding greatest for early employment years and leukemias of uncertain subtype | Schubauer-Berigan et al. 2007 (60) |
| Benzene; SES | Leukemia (non-CLL) | <15% (direction not reported) | <15% change in ERR when adjusting for benzene or SES exposure in leukemia case-control study among US nuclear workers | Daniels et al. 2013 (69) | ||
| 15 | UK NRRW (33) | SES | Leukemia | Not reported | Authors state that omitting SES adjustment had little impact on ERR/Sv | Muirhead 2009b (56) |
*
CI = confidence interval; CLL = chronic lymphocytic leukemia; CSS = cancer susceptibility syndrome; CT = computed tomography; ERR = excess relative risk; ERR/Sv = excess relative risk per Sievert; GB = Great Britain; HR = hazard ratio; INWORKS = International Nuclear Workers Study; NRRW = National Registry for Radiation Workers; SES = socioeconomic status; USRT = US Radiologic Technologists.