Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Summary Bias Assessment and Meta-Analysis.
Journal
Journal of the National Cancer Institute. Monographs
ISSN: 1745-6614
Titre abrégé: J Natl Cancer Inst Monogr
Pays: United States
ID NLM: 9011255
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
18
03
2020
accepted:
26
03
2020
entrez:
14
7
2020
pubmed:
14
7
2020
medline:
20
4
2021
Statut:
ppublish
Résumé
Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.
Sections du résumé
BACKGROUND
Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases.
METHODS
Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia.
RESULTS
Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers.
CONCLUSIONS
Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.
Identifiants
pubmed: 32657347
pii: 5869934
doi: 10.1093/jncimonographs/lgaa010
pmc: PMC8454205
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-200Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Références
J Radiol Prot. 2012 Mar;32(1):73-83
pubmed: 22392887
Health Phys. 2009 Jan;96(1):55-66
pubmed: 19066487
Lancet Haematol. 2015 Jul;2(7):e276-81
pubmed: 26436129
Radiat Res. 2011 Aug;176(2):244-58
pubmed: 21381866
J Radiol Prot. 2016 Mar;36(1):N1-7
pubmed: 26878249
Radiat Res. 2013 Mar;179(3):361-82
pubmed: 23398354
J Radiol Prot. 2016 Sep;36(3):474-489
pubmed: 27355245
Occup Environ Med. 2010 Nov;67(11):737-43
pubmed: 20798008
Radiat Environ Biophys. 2017 May;56(2):127-138
pubmed: 28337585
Int J Epidemiol. 2006 Apr;35(2):386-96
pubmed: 16269548
Stat Med. 2002 Jun 15;21(11):1539-58
pubmed: 12111919
Leukemia. 2013 Jan;27(1):3-9
pubmed: 22766784
Health Phys. 2012 Feb;102(2):173-81
pubmed: 22217590
J Occup Environ Med. 2008 Jul;50(7):791-803
pubmed: 18617835
BMJ. 2015 Oct 20;351:h5359
pubmed: 26487649
PLoS One. 2015 Feb 26;10(2):e0117784
pubmed: 25719381
Contemp Clin Trials. 2007 Feb;28(2):105-14
pubmed: 16807131
Radiat Environ Biophys. 2010 Mar;49(1):47-55
pubmed: 19823862
Br J Cancer. 2013 Nov 26;109(11):2886-93
pubmed: 24129230
Environ Health Perspect. 2015 Jun;123(6):622-8
pubmed: 25707026
Proc R Soc Med. 1965 May;58:295-300
pubmed: 14283879
J Natl Cancer Inst Monogr. 2020 Jul 1;2020(56):97-113
pubmed: 32657348
J Natl Cancer Inst Monogr. 2020 Jul 1;2020(56):133-153
pubmed: 32657349
Environ Health Perspect. 2013 Jan;121(1):59-65
pubmed: 23149165
Br J Cancer. 2017 Dec 5;117(12):1883-1887
pubmed: 28972968
Lancet Haematol. 2018 Aug;5(8):e346-e358
pubmed: 30026010
Br J Cancer. 2009 Jan 13;100(1):206-12
pubmed: 19127272
J Clin Endocrinol Metab. 2017 Jul 1;102(7):2575-2583
pubmed: 28323979
Occup Environ Med. 2011 Jun;68(6):457-64
pubmed: 20935290
Int Arch Occup Environ Health. 2008 May;81(6):777-85
pubmed: 17929049
Radiat Res. 2007 Feb;167(2):222-32
pubmed: 17390730
J Natl Cancer Inst Monogr. 2020 Jul 1;2020(56):176-187
pubmed: 32657345
CMAJ. 2011 Mar 8;183(4):430-6
pubmed: 21324846
Radiat Environ Biophys. 2014 May;53(2):405-16
pubmed: 24553629
J Natl Cancer Inst Monogr. 2020 Jul 1;2020(56):114-132
pubmed: 32657346
Environ Res. 2011 Nov;111(8):1230-5
pubmed: 21855866
Radiat Res. 2008 Dec;170(6):721-35
pubmed: 19138033
J Natl Cancer Inst Monogr. 2020 Jul 1;2020(56):154-175
pubmed: 32657350
Int J Cancer. 2016 Nov 1;139(9):1975-82
pubmed: 27405274
Am J Epidemiol. 2019 Sep 1;188(9):1581-1585
pubmed: 31145434
Br J Cancer. 2016 Feb 16;114(4):388-94
pubmed: 26882064
Radiat Res. 2015 Jun;183(6):620-31
pubmed: 26010709
AJR Am J Roentgenol. 2017 Jun;208(6):1278-1284
pubmed: 28350475
J Radiat Res. 2008 Jan;49(1):83-91
pubmed: 17690532
Radiat Res. 2017 May;187(5):513-537
pubmed: 28319463
Occup Environ Med. 2015 Dec;72(12):862-9
pubmed: 26350677
Radiat Environ Biophys. 2015 Mar;54(1):13-23
pubmed: 25315643
Int J Cancer. 2016 Jun 15;138(12):2875-83
pubmed: 26860236
Environ Health Perspect. 2017 Apr;125(4):714-720
pubmed: 27483500
Radiat Res. 2009 Apr;171(4):504-12
pubmed: 19397451
Br J Cancer. 2014 Jan 7;110(1):214-23
pubmed: 24231946
Br J Cancer. 2016 Oct 25;115(9):1105-1112
pubmed: 27623235
Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):605-13
pubmed: 18349278
J Radiol Prot. 2018 Mar;38(1):357-371
pubmed: 29313822
Occup Environ Med. 2008 Dec;65(12):843-8
pubmed: 18805884
Radiat Res. 2015 Jul;184(1):56-65
pubmed: 26121228