epidemiological studies and their role in defining dose
TRANSCRIPT
Epidemiological studies and their role in
defining dose conversion factors for radon
Aleš Froňka, Ladislav Tomášek
([email protected], [email protected])
Státní ústav radiační ochrany, v.v.i., Bartoškova 28, 140 00, Praha 4 – Nusle,
Czech Republic
Technical Meeting on the Implications of the New Dose Conversion Factors for Radon,
IAEA, 1‒4 October 2019
Radon and its short term decay productsRadon-222 is a gaseous decay product of Ra-226
from uranium-238 decay series that is normally
present in the rocks and the upper soil layers
(subsoil). Radon can be transported via variable
transport mechanisms and variable entry pathways
into buildings where it can be trapped and
concentrated to significant levels. Subsequently,
short lived decay products (Po-218, Pb-214, Bi-
214, Po-214) are being generated and attached to
aerosol particles. Aerosols can be inhaled and
deposited in the lungs where cells of the
respiratory tract might be irradiated with alpha
particles while decaying. Levels of public and
occupational exposures can vary substantially
depending on the local geology, the type of building,
its ventilation, and the behavior of the occupants.
Since the radioactive gas radon (radon-222) as a
ubiquitous source of exposure is a recognised
source of lung cancer, appropriate system of
radiation protection needs to be established and
proper tools and measures applied.
Biological effects of ionizing radiation
For protection purposes the biological effects of radiation are separated into stochastic effects
(cancer, heritable effects) and tissue reactions.
Stochastic effects - cancer and hereditary effects
- malignant disease and heritable effects for which the probability of an effect occurring
(not its severity), is regarded as a function of dose without threshold
- non-lethal transformation of an irradiated somatic cell leading to cancer in the individual
exposed after a latency period differing based on types of exposed tissues or organs
- hazard identification; dose-response assessment; exposure assessment, and risk
characterization, including identification of key uncertainties (modifying and confounding
factors, bias)
- linear non-threshold (LNT) hypothesis of the dose-response curve quantitatively
expressing the stochastic effects of radiation – the probability of the occurrence of a
stochastic effect is directly proportional to the dose received
- Quantitative Risk Assessment – dose response models based on epidemiological studies
and biological mechanisms research providing scientific based evidence
- detriment-adjusted nominal risk coefficient, including all cancers and hereditary effects
Epidemiological studies – quantitative analysis
of stochastic effects of ionizing radiation
• Study of association between risk carcinogenic factor (radon exposure) and biological
effect (cancer incidence) – quantitative assessment
• Statistical analysis of two defined populations
- population exposed to risk factor
- population with no or minimal exposure to risk factor (time integral of radon progeny intake)
- principal risk models (relative risk; absolute risk model)
The overall average lifetime excess risk of cancer and non-cancer for a general population and
for a working population can be provided for a practical system of protection.
• risk modifying factors – race, gender, age-at-exposure, attained age and time- since exposure
• lifestyle factors and inherent characteristics that can modify risk - smoking, alcohol and drug
use, diet and obesity and certain genetic conditions
• incorporation of specific modifying factors into the risk assessment process is still the subject
of research
Epidemiological studies – quantitative analysis
of stochastic effects of ionizing radiation
Types of epidemiological studies
- Cohort study (prospective) – participant selections according to attributes of observed population (study commencement – known and healthy status of persons selected and known exposure to risk factor (exposure to radon progeny concentration – long-term integrating indoor radon Measurement in case of residential radon study; personal dosimeters in case of occupational miners study)time consuming studies, large number of persons involved in observed population needed
- Case/control study (retrospective) – based on indicated cancer cases among individuals and retrospective assessment of radon progeny exposuresless time consuming studies; limited number of cases and controls; biased population construction
- Ecological study (correlation) – indicators of health status characterizing individual populations such as district, county, regional geological units, radon prone areas(strong simplification with the absence of individual data on exposures) – significantly increased risk of biased datasets
https://www.rerf.or.jp/en/
120 000 survivors population
Radiation epidemiology
- informative resource, providing a
temporal profile of leukemia and cancer
associated with the blast and a robust
data set for making quantitative
estimates of risk
Relative Risk derived from Life Span Study all cancers
Life Span Study – Atomic bombings survivors (Hiroshima and Nagasaki)
Relative Risk derived from Life Span Study all cancers
mSv mean Obs RR 90%CI
0-20 0.003 4623 1.00
20-100 0.049 1488 1.03 0.98 - 1.08
100-200 0.142 531 1.05 0.97 - 1.13
200-500 0.318 671 1.15 1.07 - 1.23
500-1000 0.679 370 1.32 1.21 - 1.45
1000-2000 1.336 278 1.77 1.60 - 1.96
2000+ 2.681 79 2.49 2.06 - 3.00
http://www.rerf.jp/top/datae.htm 12canc.dat
Statistically significant
increased RR
200-500 mSv
Relative Risk derived from Life Span Study all cancers
Epidemiological studies – factors that must be considered
when designing a residential radon epidemiology
• Accurate determination of radon exposures - past exposures estimate from current measurements - large number of study participants is needed, reducing the exposure uncertainty and increasing the statistical power of the study – long term integrating measurement using solid state nuclear track detectors (repeated measurement to identify year-to-year variations)
• Mobility: limited testing of all homes where people has lived;
• Refurbishment of housing stock (home energy retrofits): during duration of epidemiological study, existing homes are often renovated, sometimes mitigated if located in radon prone areas, thus radon measurements will be highly variable; indoor radon concentration might be lower or higher according to changes to ventilation systems, the occupancy patterns and building characteristics
• Inaccurate information on health related and lifestyle status: often a majority of the lung cancer cases (individuals) being studied are deceased or too sick to be interviewed by researchers - second-hand information are needed introducing inaccuracies:
- residence history, smoking history, genetic factors, lifestyle, exposure to other carcinogens, and home HVAC preferences
Summary of occupational radon studies of miners published
in the period of 2006–2017
Study Follow-up Miners Person-years
Lung cancers
Mean cumulative exposure (WLM)
ERR per 100 WLM (95% CI)
Colorado 1950–2005 4 137 120 437 612 794 NA
Czech Republic 1952–2010 9 978 308 910 1 141 73 0.97 (0.70, 1.33)
Czech Republic andFrance 1946–1995 10 100 248 782 574 47 1.6 (1.0, 2.4)
Eldorado 1950–1999 17 660 508 673 618 100 0.55 (0.37, 0.81)
Port Hope 1950–1999 2 645 82 999 99 16 0.21 (−0.45, 1.59)
Beaverlodge 1969–1999 10 050 NA 311 61 0.70 (0.38, 1.17)
1965-1999 NA 134 113 123 32 2.4 (0.9, 4.7)
France 1946–2007 5 086 179 995 211 37 0.71 (0.31, 1.30)
1956–1999 3 377 89 405 66 18 2.12 (0.53, 5.28)
1946–1999 5 086 153 063 159 37 0.63 (0.23, 1.22)
New Mexico 1979–2005 2 745 63 395 117 NA NA
Newfoundland 1950–2001 1 742 70 894 191 378 0.47(0.28, 0.65)
Ontario 1954–2007 28 546 805 650 1 230 21 0.64 (0.43, 0.85)
Sweden 1958–2000 5 486 170 204 122 65 2.20(0.73, 3.77)
Wismut 1946–2013 58 974
2 332 008
1 620 190
956 776
3 942
1 254
495
241
18.4
16.8
0.19 (0.17, 0.22)
0.6 (0.3, 1.0)
1.1 (0.6, 1.7)
Epidemiological studies – LEAR derived from miners cohort studies
Reference Risk model Background rates,
(ICRP reference
population)
Risk x
10-4 WLM-1
ICRP Pub. 65
(1993)
GSF model
(ICRP Pub. 65)
ICRP Pub. 60 (Japan, USA,
Puerto Rico, UK, China)
2.83
Tomasek et al
(2008)
GSF model
(ICRP Pub. 65)
ICRP Pub. 103 (Euro-
American/ Asian population)
2.7
Tomasek et al
(2008)
BEIR VI(a)
(11 studies)
ICRP Pub. 103 5.3
Czech-French ICRP Pub. 103 4.4
Exposure-age-concentration risk model
J.Marsh, 9th Conference on Protection against Radon at Home and at Work 2019
BEIR VI
ICRP65(GSF)
BEIR IV
CZ+F
Risk projection for exposure 2 WLM/year in age 18-64
Exposure 1 WLM/year
ER
R
Stochastic effects - lung cancer incidence excess relative
risk for occupational exposure and public exposure
Lung cancer
incidence excess
relative risk (RR)
for an occupational
exposure
(uranium miners
study) and public
exposure
(residential
study) to radon
(Rn-222) short-
term daughter
products
WLM
U-Miners study
Life-time
Exposure to 136 Bq.m-3
~150 mSv
General population
Study No.
Cases
Cv
Bq/m3 RR/100 Bq m-3 95% CI weight
New Jersey 480 26 1,56 0,78 3,97 4,4
Winnipeg 738 120 1,02 0,95 1,25 93,0
Missouri –1 538 63 1,01 1,42 33,1
Missouri –2 512 56 1,27 0,88 2,53 8,1
Iowa 413 127 1,44 1,05 2,59 11,1
Connecticut 963 33 1,02 0,79 1,51 25,0
Utah - South Idaho 511 57 1,03 0,80 1,55 23,0
Sweden – Stockholm 201 128 1,16 0,86 1,92 15,1
Sweden 1281 107 1,10 1,01 1,22 357,3
Southern Finland 291 213 1,28 0,79 1,78 35,3
Finland 517 96 1,11 0,94 1,31 140,1
Southwest England 982 56 1,08 0,97 1,20 346,8
Italy 384 96 1,14 0,89 1,46 62,8
Germany, eastern part 1192 74 1,08 0,97 1,20 346,8
Germany, western part 1449 50 0,98 0,82 1,17 122,4
Sweden (non-smokers) 258 79 1,28 0,95 2,05 17,3
France 688 128 1,05 0,99 1,12 923,9
Czech Republic 210 463 1,09 1,02 1,21 352,0
Shenyang, China 308 85 0,95 1,08 233,1
Gansu, China 768 223 1,19 1,05 1,47 86,1
Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies (Darby et al. 2005)
Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies (Darby et al. 2005)
Estimated excess relative risk (ERR), considering a 30 year exposure period,
70% indoor occupancy factor and the year-to-year variability in the radon
exposure.
0.16 per 100 Bq m-3
(95% CI: 0.05 – 0.31)
7148 cases of
lung cancer
14 208
controls
Cv [Bq/m3] No.
cancers RR 95%CI
<25 566 1.00 0.87-1.15
25-49 1999 1.06 0.98-1.15
50-99 2618 1.03 0.96-1.10
100-199 1296 1.20 1.08-1.32
200-399 434 1.18 0.99-1.42
400-799 169 1.43 1.06-1.92
800- 66 2.02 1.24-3.31
celkem 7148
Brit Med J 330: 223-226 (2004)
Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies (Darby et al. 2005)
Not available
30 - 100 Bq/m3
100 - 200 Bq/m3
200 - 400 Bq/m3
>400 Bq/m3
Mid-Bohemia Pluton (240 km2)
11 842 residents (epidemiological study)
Mean indoor radon concentration
Indoor radon in the Czech Republic – prospective cohort
epidemiological study
Incidence cancer cases needed in low dose epidemiological studies
Statistical power of the study
Significance level = 5% (one-tailed test)
1 case : 3 controls ratio
Statistical power =
80%
Exposure
RR
No. cases
200 mSv 1.12 3 000
100 mSv 1.06 11 500
50 mSv 1.03 45 000
Statistical power =
90%
200 mSv 1.12 4 000
100 mSv 1.06 16 000
50 mSv 1.03 62 000
Dose conversion convention, ICRP 65 (1993) - epidemiological
approach
Publication ICRP 115 Statement on Radon
DCC – dose conversion factor
• Revised nominal risk coefficient of 5 10-4 WLM-1 replaces the Pub 65 value of
2.83 10-4 WLM-1
• Upper Reference Level for homes reduces from 600 Bq m-3 to 300 Bq m-3
• Equating total detriment using ICRP Publication 103 values
Workers 4.2 x 10-2 Sv-1 12 mSv WLM-1
Public 5.7 x 10-2 Sv-1 9 mSv WLM-1
Publication 65 values
Workers 5 mSv WLM-1
Public 4 mSv WLM-1
9th Conference on Protection against Radon at
Home and at Work 16-20 September 2019, Prague
Lifetime risks in cohort studies of uranium
miners
Ladislav Tomasek SURO
Nora Fenske BfS
Dominique Laurier IRSN
Paul Demers Cancer Care Ontario
Summary of joint studies of European U-miners
study miners lung cancers mean exposure
Czech 9 979 921 61 WLM
French 5 086 159 25 WLM
German 34 994 487 47 WLM
total 50 059 1567 47 WLM
0
2
4
6
8
10
12
0 100 200 300 400 500 600 WLM
O/E Czech
French
German
Excess Relative Risk per WLM
RR = 1 + b W
b = ERR/WLM
Study ERR/WLM 90%CI
Czech 0.0104 0.0077 – 0.0142
French 0.0062 0.0027 – 0.0111
German 0.0039 0.0029 – 0.0051
p=0.0004
0
20
40
60
80
100
1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995
WLM/year
German
French
Czech
Lower ERR/WLM from more distant periods (before) reflect higher uncertainty of earlier
exposures (less or no measurements) overestimation of exposures (measurements conducted at
workplaces with higher concentrations) exposure rate (cell killing because of high doses)
partly effect of time since exposure.
Period specific ERR/WLM (in two exposure windows)
RR= 1 + bbefore Wbefore + bafter Wafter
Study
Cut
points ERR/WLM
before
90%CI ERR/WLM
after
90%CI
Czech 1953 0.0069 0.0041 – 0.0107 0.0210 0.0147 – 0.0305
French 1956 0.0016 -0.0009 – 0.0057 0.0219 0.0120 – 0.0358
German 1964 0.0027 0.0017 – 0.0038 0.0206 0.0142 – 0.0282
p = 0.012 p = 0.985
0.0210 0.0167 – 0.0261
CV=14%
0
1
2
3
4
0 1 2 3 4 5 6 7
ER
R/1
00W
LM
Entire Cohorts
Low Exp
Excess relative risk per WLM in cohorts reported by UNSCEAR
CZE ELD FRA NFL ONT SWE WIS
RR = 1 + b W
RR = 1 + blow Wlow + bhigh Whigh
Mean annual levels (WL) in uranium mines
0
1
2
3
4
5
6
7
1945 1950 1955 1960 1965 1970 1975 1980 1985 1990
WL
WIS
FRA
CZE
ONT
<0.5
BEIR VI model
RR = 1 + (b5-14 W5-14 + b15-24 W15-24 + b25+ W25+) a(j) c(k)
(attained age categories) j = ≤54, 55–64, 65–74, ≥75
(exposure rate categories) k = <0.5, 0.5–1, 1–3, 3–5, 5–15, ≥15 WL
B2 UNSCEAR model
RR = 1 + (blow Wlow + bhigh Whigh) a(j) t(k)
low <0.5 WL
high >0.5 WL
(attained age categories) j = ≤54, 55–64, 65–74, ≥75
(time since exposure categories) k = 5-14, 15-24, 25+
UNSCEAR 2019 Appendix B
BEIR VI and B2 models
11 cohorts Czech Wismut Eldorado Ontario
Lung cancers 2864 1161 3942 618 1246
BEIR VI B2 BEIR VI B2 BEIR VI B2 BEIR VI B2
Age specific
ERR/100WLM
<55 7.68 12.71 6.47 7.22 2.31 3.46 6.11 9.36
55-64 4.38 4.22 1.81 2.72 1.11 1.61 9.90 2.92
65-74 2.23 1.47 1.42 1.28 0.76 1.11 5.01 1.06
75+ 0.69 1.17 1.36 1.05 0.74 1.12 1.16 1.11
Time since exp
<15 1 1 1 1 1 1 1
15-24 0.78 0.96 0.77 0.89 0.79 0.74 0.47
25+ 0.51 0.71 0.41 0.57 0.54 0.56 0.29
Exp.rate
<0.5 WL 1 1 1 1 1 1 1 1
>0.5 WL 0.11
0.49
0.10 0.63
1.29
0.88 0.16
0.61
0.22 1.05
0.16
0.36
model cohort LTR0 104 LEAR/WLM SE ICRP male and female rates
BEIR VI 11 cohorts 0.048 5.6 1.3 B2 11 cohorts 0.048 7.0 1.5 BEIR VI Czech 0.048 3.9 1.0 B2 Czech 0.048 4.5 1.1 BEIR VI Wismut 0.048 2.4 0.6 B2 Wismut 0.048 3.2 0.6 BEIR VI Eldorado 0.048 7.5 3.0 B2 Ontario 0.048 6.7 1.7
ICRP male rates BEIR VI 11 cohorts 0.061 7.0 1.6 B2 11 cohorts 0.061 8.7 1.8 BEIR VI Czech 0.061 5.0 1.3 B2 Czech 0.061 5.6 1.3 BEIR VI Wismut 0.061 3.0 0.7 B2 Wismut 0.061 4.0 0.8 BEIR VI Eldorado 0.061 9.6 3.8 B2 Ontario 0.061 8.3 2.1
Lifetime risks
Thank you for your attention!
This work was partly funded by
the Czech Ministry of the Interior
Project MV-25972-2/OBV
and by the European Commission
Project 516483