Radiation Epidemiology. Radon in homes

Transcription

1 Radiation Epidemiology Radon in homes PD Dr. Michaela Kreuzer 1

2 Radon in homes Air exchange with outdoor air (ventilation habits, Insulation of windows) Floor level Insulation of the basement Radon content in the soil 2

3 Frequency distribution of indoor radon concentrations in Bq/m³ in Germany 1500 Number of dwellings Mean 50 Bq/m Bq/m 3 3

4 History of radon epidemiology Studies in underground miners Ecological studies (misleading) Case-control studies generation I without individual radon measurements Case-control studies generation II and III: - individual radon measurements, control for smoking Pooling of individual data of case-control studies 4

5 Ecological radon studies I Lung cancer mortality rate Radon in homes in Bq/m 3 Negative correlation!

6 Ecological radon studies II Lung cancer mortality rate Proportion of smokers High positive correlation

7 Ecological radon studies III Proportion of smokers Radon in homes in Bq/m 3 Negative correlation!

8 Ecological studies Definition: Correlation of geographically aggregated lung cancer rates with mean radon concentrations from that geographic areas Limitations - no individual data - no control for potential confounders - Ecological fallacy 8

9 Case-control studies Individual radon measurements individual information on smoking German case-control study Kreienbrock et al. 2001; Am J Epidemiol Kreuzer et al. 2003, Epidemiology Wíchmann et al. 2005, Health Phys 9

10 Study Design I Two case-control studies (East/West Germany) - 1 : 1 (frequency-) matching (age, gender, area) Study Period to 1996 Inclusion Criteria - age < 75 years - living in study region - living in Germany since never employed at the WISMUT SDAG 10

11 Geologic radon potential and study regions 5 Dortmund/Bochum 4 Essen/Duesseldorf 10 Soest/Hochsauerld 15 Nordthueringen 22 Riesa/Kamenz 21 Oberlausitz 19 Nordwestsachsen 1 Aachen 2 Bonn/Koeln 3 Bergisches Land 14 Erfurt/Gera/Jena/Suhl/Weimar 16 Westthueringen 17 Ostthueringen 20 Dresden 23 Dresdner Umland 18 Erzgebirge 8 Hunsrueck/Westerwald 9 Eifel 11 Oberfranken 7 Saarland 6 Rheinland-Pfalz 12 Mittelfranken 13 Oberpfalz/Niederbayern

12 Study Design II Incident cases of lung cancer (n 4,500) - recruited from 15 study clinics - histological or cytological confirmation Population controls (n 4,500) - randomly selected from either population registers or by random digit dialing Interview - personal interviews by trained interviewer 12

13 Residential History only duration and place of residence Measurement and questionnaire Interviewing of subsequent tenants present dwelling Reconstruction period 35 ys 5 ys Birth Interview 13

14 Standardized Questionnaire Residential History - all adresses of former residences - type of house (old, new, etc.) - type of windows (insulation, etc.) - ventilation habits (winter, summer, night, day) - type of basement (insulation, etc.) - level of floor - occupancy (hours spent in each room) 14

15 Standardized Questionnaire - Occupation (Asbestos exposure) - Active smoking (smokers) - Passive smoking (non-smokers) - Diet - Family history of cancer - Previous lung diseases or cancer 15

16 Measurement of radon concentrations Short-term measurement (3 days) - charcoal canisters Long-term measurement (1 year) - alpha-track detectors Both dosimeters were placed in - the bedroom and the main living room - in the current and in all former residences (at least 25 years past) Daily and saisonal variation of radon concentrations in homes!! 16

17 Seasonal variations in median radon concentrations 17

18 Assessment of radon exposure For each residence - average of radon concentrations in the bedand living-room weighted by the proportion of time spent in these rooms Time-weighted average of radon concentrations in the period 5-35 years before interview - all residences in the 5-35 year period - corrected for changes in ventilation or other - missing data imputed by study specific mean 18

19 Statistical Methods Conditional logistic regression (stratified by age, gender and region) Odds Ratio (OR) and 95% confidence intervals Adjustment for - smoking (packyear, time since quitting smoking) - asbestos exposure (yes/no) Linear Risk model: RR = 1 + β x β = ERR (Excess Relative Risk) per unit radon concentration 19

20 Lung cancer risk by time weighted average radon exposure during the 5-35 years prior interview in Germany Radon Bq/m 3 Cases Controls OR 95% CI OR adj 95% CI ,532 2, Reference 1.00 Reference , ( ) ( ) > ( ) totals 2,963 4,232 ERR per increase 0.00 of 100 Bq/m 3 (-0.03,0.10) 0.10 (-0.02, 0.30) OR adj : Odds ratio adjusted for age, sex, and region, smoking (log(pack-years+1), years since quitting, other tobacco products), occupational asbestos (exposed vs. non exposed) ERR: Excess relative risk per increase of 100 Bq/m 3 20

21 Risk of lung cancer in German studies Wichmann et al. 2005, Health Physics Relatives Risiko (95% CI) 2 1,5 1 ERR per 100 Bq/m 3 = 0,10 95% CI (-0,02 bis 0,3) 0, Radon (Bq/m ³) 21

22 Excess Relative Risk per 100 Bq/m 3 in published single studies 0,8 1,5 0,6 0,4 0,2 0-0,2 Kanada Shenyang Deutschl. West Connecticut Utah Frankreich Missouri I Missouri II England Deutschl. Ost Tschech. Rep. Schweden I Finnland Italien Iowa Gansu Österreich New Jersey Schweden II Italien II Schweden III Finnland II Spanien 22

23 History of radon epidemiology Studies in underground miners Ecological studies (misleading) Case-control studies generation I without individual radon measurements Case-control studies generation II and III: - individual radon measurements, control for smoking Pooling of individual data of case-control studies 23

24 Scand J Work Environ Health 2006; 32 suppl 1: 1-80 British Medical Journal 2005; 330:

25 Open questions Exposure-response-relationship? Threshold dose? Risk among never-smokers? Effect modification? Combined effect of smoking and radon? Number of radon-induced lung cancers?n 25

26 Number Study Cases Controls 13 studies 9 countries cases contr. Austria Czech Republic England Finland (nationwide) Finland (South) France Germany (East) Germany (West) Italy Spain Sweden (nationwide) Sweden (never-smoker) Sweden (Stockholm)

27 Radon exposure Radon measurements for 23 years on average, 77% of the 30 year period Missing values imputed by study specific mean of the controls Time-weighted average of radon concentrations 35-5 years before diagnosis Mean radon: cases 104 Bq/m 3, controls 97 Bq/m 3 n 27

28 Statistical Methods Linear Risk model: RR = 1 + β x β = ERR (Excess Relative Risk) pro unit radon concentration Adjusted for study, age (5-year groups), sex, region, smoking in 20 groups [never-smokers; current cigarette smokers (<15/15-24/25+ cigs/day), subdivided by age started (<15/15-17/18-20/21+ years); ex-smokers (<10/10+ years, subdivided by amount smoked (<15/15-24/25+ cigs/day); others] 28

29 Relative Risk in different exposure categories relative to 0 Bq/m 3 Radon in number Bq/m 3 Cases controls Relative Risk 95 % CI < ,00 0,87 1, ,06 0,98 1, ,03 0,96 1, ,20 1,08 1, ,18 0,99 1, ,43 1,06 1, ,02 1,24 3,31 Insgesamt

30 Risk of lung cancer according to radon 3 2,5 Relatives Risiko (95% CI) 2 1,5 1 RR = 1 ERR pro 100 Bq/m 3 = 8,4 % 95% KI = (3 % - 16 %) 0, Radon (Bq/m ³) 30

31 Exposure-response-relationship Comparison of different models RR = 1 + 0, X RR = exp(0, X) RR = 1 + 0, X + 0, X 2 linear models with different assumptions for a threshold none of these models provided a better fit than the linear model without threshold 31

32 Risk of lung cancer according to radon below recommended action levels 3 Relatives Risiko (95% CI) 2,5 2 1,5 1 < 200 Bq/m 3? RR = 1 Restriction to individuals with radon concentrations < 200 Bq/m 3 ERR per 100 Bq/m 3 = 14 % 95 % KI: 0,4%- 30% Radon in Anzahl Bq/m 3 Fälle Kontr. RR 95 % KI < , ,20 1,03 1,30 0, Alle Radon (Bq/m ³) 32

33 Effect Modification Is there a difference in the ERR per 100 Bq/m 3 with respect to? - sex - age - study - smoking status 33

34 Risk of lung cancer according to radon by smoking status 3 ERR = 11 % 3 ERR = 8 % 3 ERR = 7 % 2,5 2,5 2, ,5 1,5 1, , , , Lifelong non-smoker Ex-smoker Current smoker 34

35 Random uncertainties in retrospective estimation of exposure Home 1 Home 2 Home 3 Home ys 35 ys Uncertainties due to imputation of missing values Uncertainty due to variation of radon concentrations in the same dwelling in different years external data showed substantial variation 35

36 Relative risk of lung cancer according to measured and corrected radon concentration 3 3 Relatives Risiko (95 % KI) 2,5 2 1,5 1 Relatives Risiko (95 % CI) 2,5 2 1,5 1 0, , Observed Radon (Bq/m3) Corrected Radon (Bq/m3) ERR / 100 Bq/m 3 = 8,4 % 95% KI (3-16), p = 0,0007 ERR / 100 Bq/m 3 = 16,0 % 95% KI (5-30), p = 0,008 36

37 Risk with and without adjustment for uncertainties in exposure Study ERR/ 100 Bq/m 3 95% CI. EUROPE (without) 0,08 0,03 0,16 Regression calibration 0,16 0,03 0,31 NORTH AMERICA (without) 0,11 0,00 0,28 > 25 years covered by measurement 0,21 0,03 0,52 CHINA (without) 0,13 0,01 0,36 > 30 ys in current residence 0,32 0,07 0,91 37

38 Cumulative risk of lung cancer death by 75 years by radon for smokers and non-smokers Radon concentration Deaths per 1000 in Bq/m 3 lifelong nonsmokers Deaths per 1000 smokers ) A smoker of cig/day has 25fold higher risk of lung cancer than a lifelong nonsmoker 2) ERR per 100 Bq/m 3 = 16% 38

39 Radon in the home accounts for about 9% of deaths from lung cancer and about 2% of all deaths from cancer in Europe Darby et al

40 Radon in homes accounts for 5 % (95 % CI: %) of deaths from lung cancer in Germany in comparison to outdoor air of 9 Bq/m 3 Menzler et al Radon in homes causes lung cancer deaths per year (95% KI: ) 40

41 Conclusion The exposure-response-relationship seemed to be linear, with no evidence of a threshold dose There was a significant exposure-response-relationship even below currently recommended action levels ERR per 100 Bq/m 3 16 % ERR per 100 Bq/m 3 nearly similar for never-smokers and current smokers, therefore the absolute risk to smokers is much greater than to lifelong non-smokers 41

42 Public Health Impact Lung cancer is the leading cause of cancer Radon accounts for about 9% of all lung cancers in EU About 90% of all radon-induced lung cancers occur below 200 Bq/m 3 not only avoiding extreme exposures is important, but also reducing average exposures Low concentrations can usually be ensured in new buildings at reasonable or low cost and in existing buildings at moderate cost 42

43 WHO Radon Handbook - Risk Assessment - Measurement - Prevention and Mitigation - Cost-Effectiveness - Risk communicationn - National Radonprograms 43

44 National Reference Level A Reference Level is the annual mean radon concentration in homes above which it is strongly recommended - or legally required - to reduce the radon concentration. Protective measures may also be appropriate below the Reference Level Recommendation: 100 Bq/m 3 If the level cannot be implemented for country-specific reasons the chosen Level should not be higher than 300 Bq/m 3 44