Background Ionizing Radiation and theRisk of Childhood Cancer Results from Recent Studies

Ben Spycher
Institute of Social and Preventive Medicine
University of Bern

8th Oct. 2016, CSRP 2016, Fukushima

Outline>>>>>

Sources of natural radiation
Limitations of different study designs
Brief review of studies on childhood leukaemia and• Radon gas• Terrestrial gamma and cosmic rays
The Swiss National Cohort study
Conclusions

2

Background>Lessons from atomic bomb survivors:— High doses can induce leukaemia— Children are particularly susceptible— Short latency for childhood leukaemia>>

Effects of low doses (<100 mSv) uncertain
Current risk models predict that natural background radiation
contributes importantly to risk of leukaemia in children— UK study 15-20% (Little et al, 2009)— French study 4-20% (Laurent et al, 2013)>

Large studies are needed to verify this (Little et al, 2010)3

Effective dose from natural sources(worldwide average)

UNSCEAR Report 2000, Annex B

4

RBM dose from natural sources(UK)
Cumulative RBM dose (conception to 15 yrs) in UK: 21 mSv

Based on Kendall et al. J Radiol Prot 20095Studies on domestic radon
Ecological studies
First author

Year

Country

Area units

Lucie
Henshaw
ButlandAlexander
MuirheadCollmanForemanRichardson
ThorneKohli
Evrard1989 UK
22 counties
1990 International 13 countries
1990 International 7 countries
1990 UK
22 counties
1991 UK
22 counties (459 districts)
1991 USA
3 groups (100 counties)
1994 UK
2 groups (4 counties)
1995 UK402 districts
1996 UK
2 groups
2000 Sweden
13 municipalities
2005 France
95 départements (443 zones)

Exposure

Results
No. of Incidence/cases Mortality
Indoor concentration
187
I+Indoor concentration
I+
Indoor concentration
I(+)
Indoor concentration
I+
Indoor concentration
I(+)
Water supply concentration
1194
M+
Indoor concentration
245
I(-)
Indoor concentration
6691
I(+)
Indoor concentration+
AML onlyI
Ground radon levels
22I+
Indoor concentration
5330
I
ALL (+), AML +6

Studies on domestic radon
Case-control studies
AuthorYear

Stjernfeldt
Lubin
KaletschSteinbuch
Maged
UKCCS
Yoshinaga
Raaschou-Nielsen
Kendall

1987
1998
1999
1999
2000
2002
2005
2007
2013

Country

Exposure
Registerbased
SwedenNo
Measured indoor conc.
USANo
Measured indoor conc.
GermanyNoMeasured indoor conc.
USA+CanadaNo
Measured indoor conc.
EgyptNo
Measured indoor conc.
UKNo
Measured indoor conc.
JapanNo
Measured indoor conc.
Denmark
Yes
Modelled indoor conc.
UKYes
Predicted indoor conc.

TimingDiagnosis>70% time
Residence of longest stayDiagnosis (at least 5 yrs)
Birth to diagnosis
Diagnosis
Birth to diagnosis
birthNo. Cases

Results

7505
82
173 AML
50951
255
1153
9058

(-)
(+)
(+)
(~)
+- ALL++ ALL(+)

7Studies on gamma radiation
Ecological studies
First author Year Country
Mason
TirmarcheHatch
Muirhead
AuvinenRichardson
Evrard1974 USA1988 France
1990 USA
1992 UK
1994 Finland
1995 UK
2006 France

Area units

ExposureResults
No. Incidence/Cases mortality
High altitude areas vs. national rate High altitude
327
M
(~)
5 départements vs. national rate
High gamma
391
M(~), + for 1 dép.
69 study tracts
dose rate gamma
49
I+22 counties (459 districts)
dose rate gammaI(+) county, (-) district
137
134
455 municipalities
Effective dose Cs, Cs
182I(+)
459 districts
dose rate gamma radiation 6691
I(~)
95 départements (443 zones)
dose rate gamma + cosmic 5330
I(~)

Case control studies
First author Year Country RegisterExposure
TimingNo. Cases
basedAxelson
2002 Sweden
Residence in alum shale concrete house birth to diagnosis
312
NoUKCCS
2002 UK
Measured indoor dose rates gamma
diagnosis
2165
NoKendall2013 UK
Dose rate gamma + cosmic (district mean) birth
9058
Yes

Results+(~)+8

UK record-based case-control study(Kendall 2013)>>>>9058 Cases of leukaemia, 11 912 controls
Cumulative dose since birthRadon: predictive map based on 400 000 measurements
Gamma: Mean dose rates in 459 County Districts

RR per mGy:
1.09 (1.02-1.17)→ 9% increase in risk
per mGy Gamma
doseKendall et al. Leukemia 2013

9Swiss census-based cohort study(Hauri 2013; Spycher 2015)>>>

Cohort study including all children aged <16 years in national
censuses 1990, 2000:
N = 2.1 million
Cases of childhood cancer identified from Swiss Childhood
Cancer Registry (SCCR)
Exposure assessed at census (entry into the cohort)Study period

Diagnosis
Death
16th birthday
Emmigration

No event10

Swiss National Cohort

Spoerri et al. Int J Public Health 2010

11

Swiss National Cohort

Swiss Childhood Cancer Registry(SCCR)• Nationwide coverage• Completeness >91% since 1985(>95% for recent periods)

Spoerri et al. Int J Public Health 201012

Identifying incident cancer cases
Swiss Childhood Cancer
Registry (SCCR)

3,502 Eligible Patients
Diagnosed 1990-2008
1,288 Patients
Diagnosed before or
Born after Census
2,214 Potential Incident Cases
424 Unlinked
Patients
1,790 Patients Linked to the
Swiss National Cohort

1,782 Patients Included inTime to Event Analysis8 Excluded
4 with Uncertain Place ofResidence at Census
4 with Recorded Emigration
before Diagnosis
13

Predicting indoor radon concentrations
Measurements: 44’631
Predictors (categories):•Soil texture (3)•Tectonic units (6)•Housing type (3)•Urbanisation (3)•Floor (5)•Year constructed (5)Validation: R2=0.20

Hauri et al. J Environ Radioact. 2012; Hauri et al. Indoor Air. 201314

Measurements of terrestrial gamma
radiation
Measurements:•Airborne GR spectrometry(10% of land surface)•In situ GR spectrometry(166 sites)•

In situ dose ratemeasurements using
ionisation chambers(837 sites)•Laboratory measurementsof rock/soil samples(612 sites)⇒ 1 site per 25km

Rybach et al. J Environ Radioactivity 2002; Rybach et al. IAEA-Tecdoc-980 199615

Prediction terrestrial gamma & cosmic
radiation

Rybach et al. J Environ Radioactivity 2002

16

Results for indoor radon concentration

Hauri et al. Env Health Perspect 201317

Results for dose rate gamma + cosmic
Outcome

Dose rate

Leukemia

CasesIRa

HR (95% CI)b<100 nSv/h201

3.22

1.00

100 - <150 nSv/h

288

3.27

1.02 (0.85, 1.22)

150 - <200 nSv/h

30

3.30

1.03 (0.70, 1.51)≥200 nSv/h

11

6.53

2.04 (1.11, 3.74)<100 nSv/h

158

2.53

1.00

100 - <150 nSv/h

225

2.56

1.01 (0.82, 1.24)

150 - <200 nSv/h

24

2.64

1.05 (0.68, 1.61)≥200 nSv/h

9

5.34

2.12 (1.09, 4.16)

ALL

a Per 100’000 person yearsb Adjusting for sex and birth year

Spycher et al. Environ Health Perspect; in press

18

Results for dose rate gamma + cosmic
Outcome
Leukemia

Dose rate

CasesIRa

HR (95% CI)b<100 nSv/h

201

3.22

1.00

100 - <150 nSv/h

288

3.27

1.02 (0.85, 1.22)

150 - <200 nSv/h

30

3.30

1.03 (0.70, 1.51)≥200 nSv/h

11

6.53

2.04 (1.11, 3.74)

HR per 100 nSv/h: 1.25 (0.90-1.75)

Spycher et al. Environ Health Perspect; in press

19

Results for cumulative dose(gamma + cosmic)>

Cumulative dose assuming stable residence since birth
All children
Outcome

Stable place of residence

HR per mSv (95% CI)P

HR per mSv (95% CI)

PLeukemia

1.036 (0.997, 1.077)

0.075

1.046 (0.999, 1.096)

0.054

ALL

1.037 (0.990, 1.086)

0.124

1.049 (0.994, 1.107)

0.084

Spycher et al. Environ Health Perspect; in press

20Comparison with UK study (Kendall 2013)>

Risk increase per mSv cumulative dose from indoor exposure
Swiss Study(530 cases)

UK study(9’058 cases)

Leukemia

5% (0% to 10%)9% (2% to 17%)ALL

5% (-1% to 11%)

10% (2% to 19%)>

Excess risks are comparable and compatible with current riskmodels>

Swiss study much smaller but has comparable precision:— Cohort study vs. case control (1:1)— Wider exposure range (up to 50 mSv, median 9.12 mSv)
— Poor spatial exposure resolution in UK study (County district means)

Spycher et al. Environ Health Perspect; in press

21

Other recent studies: Finland>

1,093 cases of leukaemia>

3,279 controls(age- and sex matched)>

Terrestrial gamma radiation(indoor)>

Exposure based on fullresidential history

Nikkila et al. Int J Cancer 201622

Other recent studies: France>

Incidence study:
36,326 municipalities
9,056 leukaemia cases>

Case-control study:
2,763 leukaemia cases
30,000 controls>

Radon, terrestrial gamma
and cosmic(1×1 km resolution)>

Exposure at diagnosis

Results of incidence study

Demoury et al. Environ Health Perspect Epub ahead of print

23

Conclusion>

Evidence from ecological and conventional cases-control
studies is inconclusive.

>

More recent register-based case-control studies and cohort
studies suggest that background radiation contributes to therisk of childhood leukaemia. -> Exception France
Excess risks are compatible with risk models developed
using data from atomic bomb survivors supporting greater
susceptibility of children to radiation-induced leukaemia also
at low doses. -> Exception France>>

Obtaining accurate exposure measurements on large,
representative samples remains the greatest challenge.

>

More large studies will be needed to obtain better estimatedchildhood leukaemia risks associated with low dose radiation.
24

Acknowledgements

Swiss National Cohort Study (SNC): F Gutzwiller, M Bopp, M Egger, ASpoerri, M Zwahlen, N Künzli, F Paccaud, M Oris
Swiss Childhood Cancer Registry (SCCR): C. Kuehni, V Pfeiffer, VMitter, P Wölfli, M Spring, S Parvinder, M Sturdy, E Kiraly, K Flandera
Swiss Peadiatric Oncology Group (SPOG): RA Ammann, R Angst, MAnsari, M Beck Popovic, E Bergstraesser, P Brazzola, J Greiner, MGrotzer, H Hengartner, T Kuehne, K Leibundgut, F Niggli, J Rischewski,
N von der WeidFunding:• Swiss Federal Office of Public Health• Swiss National Science Foundation• Cancer Research Switzerland