TITEL DER VERANSTALTUNG TITEL DER...
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CANUPIS Childhood Cancer and Nuclear Power Plants in Switzerland Matthias Egger, MD Professor of Epidemiology and Public Health Institut of Social- und Preventive Medicine (ISPM) University of Bern, Switzerland [email protected] www.ispm.ch
Transcript of TITEL DER VERANSTALTUNG TITEL DER...
CANUPISChildhood Cancer and Nuclear Power Plants in Switzerland
Matthias Egger, MD
Professor of Epidemiology and Public HealthInstitut of Social- und Preventive Medicine (ISPM)University of Bern, [email protected]
Presenter
Presentation Notes
Matthias Sehr geehrte.... Wir freuen uns, Ihnen heute die Resultsate der CANUPIS Studie vorzustellen. In einem multidisziplinären Team haben wir in den letzten Jahren intensiv für diese Studie gearbeitet und sind überzeugt, dass wir diese wichtige Fragestellung so sorgfältig und seriös untersucht haben, wie dies in der Schweiz im Moment überhaupt möglich ist. Voranstellen möchten wir, dass wir heute als Wissenschaftler dastehen. Wir werden Ihnen Fragestellung, Studienmethodik und Resultate vorstellen, und Ihre diesbezüglichen Fragen gerne beantworten. Für die politischen Implikationen der Resultate verweisen wir an → BAG, Bundesrat, Parlament, Parteien, Schweizervolk Ebenso wollen wir vorausschicken, dass wir keine Kinderonkologen sind, aber auch keine Strahlenbiologinnen oder Strahlenphysiker – auch für diese Fragen wenden Siesich gerne an Fachpersonen. Zuerst wird Ihnen Claudia Kuehni, Leiterin des Schweizer Kinderkrebsregisters, die Hintergründe und Methodik der Studie vorstellen, anschliessend werde ich ihnen die Resultate zeigen und erklären, wie diese berechnet wurden.
2http://ije.oxfordjournals.org/content/early/2011/07/11/ije.dyr115.full.pdf+html
25. Juli 2011 3
> Case-control study (3 controls per case)
> 593 children aged 0-4 years with leukemia,1766 controls, 16 nuclear power plants (NPPs)
> Geocoding of residence at the time of diagnosis
> Odds ratio 2.19 (lower confidence limit 1.51) in 5km zone around NPPs
Presenter
Presentation Notes
Eine im Dezember 2007 veröffentlichte Studie aus Deutschland, richete das öffentliche Augenmerk auf Kernkraftwerke als mögliche Quelle ionisierender Strahlung. Die Studie untersuchte 593 Vorschulkinder mit Leukämie und 1766 gesunde Kontrollen mit Wohnort in der Umgebung von 16 deutschen KKWs und fand eine statistisch hochsignifikante Erhöhung des Leukämierisikos bei 0-4-Jährigen Kindern im 5 Umkreis eines KKWs. Die Odds ratio von 2.19, entspricht mehr als einer Verdoppelung des Risikos. Auhc in der Schweizer Bevölkerung und im Parlament wurde diese Studie heiss diskutiert, so dass BAG und Krebsligabeschlossen, die Sache auch in der Schweiz untersuchen zu lassen. (17 expected, 20 attributable)
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Methodological issues in German study(KiKK Study)
> Selection of controls by municipalities— 16% of municipalities near NPPs did not provide data— 15% of addresses in controls were incorrect— Selection bias possible
> No control for potential confounders> Place of residence at diagnosis, rather than at birth
Presenter
Presentation Notes
Die KiKK Studie war eine Fall-Kontrollstudie. Für jedes erkrankte Kind lieferten die Gemeindeschreibereien 3 Kontrolladressen von gesunden Kindern an die Studienzentrale. Dieses Vorgehen bietet Raum für eine Verzerrung der Resultate, im epidemiologischen Jargon Selektionsbias genannt. In der Tat lieferten 16% derKKW- Standortgemeinden gar keine Adressen und 15% der Adressen waren falsch, das heisst, die Kontrollkinder wohnten zum relevanten Zeitpunkt gar nicht in der Gemeinde. Die Kikk Studie konnte ausserdem keine Confounders berücksichtigen. Confounders sind Faktoren, die in der Nähe von KKWs gehäuft vorkommen und per se krebserregend wirken könnten. zB Starkstromleitungen. Drittens analysierte die deutsche Studie, wie die meisten früheren, den Wohnort zum Zeitpunkt der Krebsdiagnose. Wir wissen, dass Kinder vor der Geburt und in den ersten Lebensjahren besonders strahlenempfindlich sind und dass eine Latenzzeit besteht zwischen dem Einwirken einer Exposition und der Entwicklung von Krebs. Deshalb wäre es sinnvoller den Wohnort vor der Erkankung zu untersuchen.
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Swiss Study
> Nation-wide cohort study— All children resident in Switzerland (1.3 million
children, 21 million person-years)
— All children with cancer 1985-2009 from national childhood cancer registry (www.childhoodcancerregistry.ch)
— Selection bias excluded
> Geocoding of all addresses at birth and diagnosis> Adjustment for potential confounders
Presenter
Presentation Notes
In CANUPIS versuchten wir, Schwächen früherer Studien zu vermeiden: Das Studiendesign war nicht eine Fall-Kontrollstudie wie in Deutschland oder eine geographische Studie wie in anderen Ländern, sondern eine nationale Kohortenstudie. Daten zur Studienpopulation kamen aus der Schweizer Nationalkohorte, einem anonymen Datensatz aller Einwohner der Schweiz. Wir konnten Wohnadressen von 1,3 mio Kinder, und Angaben zu 21 mio Lebensjahren auswerten. Erkrankungsfälle wurden aus dem nationalen Kindnerkrebsregister identifiziert. Durch die Verwendugn dieser nationalen, vollständigen Datensätze konnte ein Selektionsbias vermieden werden. Wir konnten exakte Adresse n, dh Stasse und Hausnummer, nicht nur den Gemeindemittelpunkt wie in vielen anderen Studien. Auch Confounders wurden geocodiert und analysiertt Und vor allem untersuchten wir primär den Wohnort bei Geburt. Der Wohnort bei Diagnose war eine Nebenanalyse zum Vergleich mit internationalen Daten..
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Existing and planned nuclear installationsand population density
Presenter
Presentation Notes
Diese Karte zeigt die untersuchten Orte: Wir berücksichtigen erstens alle Kernkraftwerke (grüne Dreiecke): in Mühleberg, Gösgen, Leibstadt und Beznau I und II In eine zweite Analyse schlossen wir zusätzlich zu den KKWs auch die Forschungsreaktoren und Zwischenlager ein, in Genf, Lausanne, Lucens, Basel und Würenlingen. Eine dritte Analyse untrsuchte die Orte, an denen KKWs geplant, aber nicht gebaut wurden. Verschiedene Studien im Ausland hatten an solchen Orten ein erhöhtes Krebsrisiko gezeigt, welches nicht auf Strahlung, sondern auf andere, diese Orten gemeinsame Faktoren zurückgeführt wurde. Die kleine Karte unten mit der Bevölkerungsdichte zeigt, dass all diese Anlagen alle in stark besiedelten Gegenden der Schweiz liegen.
The Swiss Childhood Cancer Registry
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Anzahl Fälle in 5 km Zone
I
II
IIIIV
7Red points indicate residences of cases – moved at random for presentation
<5 km
5-10 km
10-15 km
>15 km
Presenter
Presentation Notes
Wenn wir die Daten der ganzen Population wieder in die Karte eintragen merken wir, dass diese Anhäufungen primär dort vorkommen, wo auch viele Kinder wohnen. Für die Analyse müssen wir also Anzahl erkrankter Kinder durch die Anzahl in dieser Zone verbrachter Lebensjahre teilen,. Das gibt dann das Risiko für eine K rebserkrankung in dieser Zone, das wir nun zwischen verschiedenen Zonen vergleichen können. Wort an Matthias übergeben.
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Results
> Leukemia in children <5 years> Residence at birth> Comparision of expected with observed number
of leukemia cases> Multivariate Poisson regression
— Controlled for age, sex, year of birth
— Incidence rate ratios
> Sensitivity analyses and confounder adjusted analyses
Observed and expected cases(expected based on zone IV rate)
Zone Observeda
Person-yearsb
Ratea/b x100‘000
Expected6,75 x b x 100‘000
I 8 100,032 8.00 6.8
II 12 301,091 3.99 20.3
III 31 419,362 7.39 28.3
IV 522 7,737,459 6.75
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Observed leukemia cases, person-years, rates, and expected cases in children aged <5 years, 1985-2009
Expected versus observed: Nuclear power plants
Zone Expected Observed DifferenceI 6,8 8 +1,2II 20,3 12 -8,3III 28,3 31 +2,7IV 522 522 0
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Observed and expected leukemia cases in children <5 years, 1985-2009
Relative rates:Nuclear Power Plants
Zone Expected Observed Relative Rate(observed/expected)
I 6.8 8 1.18
II 20.3 12 0.59
III 28.3 31 1.09
IV 522 522 1.00
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Observed and expected leukemia cases in children <5 years, 1985-2009
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Relative rates: Planned but not built NPPs
IIIIIIIV
Relative Rate
IIIIIIIV
Poisson regression model for children with leukemia aged <5 years, 1985-2009
(95% confidence interval)
Presenter
Presentation Notes
The study was criticised for - potential selection bias, because communities in the vicinity of NPPs did not cooperate well For lack of adjustment for confounders And for looking only at residence at diagnosis. Considering that there is a lag time of several years between exposure to ionising radiation and development of cancer, residence prior to diagnosis, particularly during the intrauterine development and the first year of life, would be more informative.
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IIIIIIIV
Relative rates: NPPs and all nuclear installations
IIIIIIIV
1.20 (0.60–2.41)
1.15 (0.83–1.59)
Tests for trend >0.30
NPPs
All nuclear installations
Poisson regression model for children with leukemia aged <5 years, 1985-2009
Presenter
Presentation Notes
The study was criticised for - potential selection bias, because communities in the vicinity of NPPs did not cooperate well For lack of adjustment for confounders And for looking only at residence at diagnosis. Considering that there is a lag time of several years between exposure to ionising radiation and development of cancer, residence prior to diagnosis, particularly during the intrauterine development and the first year of life, would be more informative.
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Additional analyses
Main analysis
Down-wind exposure zones
Excluding children >50 km from NPPs
Period of complete registration
Excluding children born abroad or <1985
Alternative calculation of person years
Beznau and Leibstadt excluded
Mühleberg excluded
Gösgen excluded
Calendar period 1985-1994
Calencar period 1995-2009
Children remaining at place of birth
Poisson regression m
odel for children w
ith leukemia aged <5 years, 1985-2009
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
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Considered confounders
> Background ionising radiation(cosmic, terrestric, chernobyl fallout)
> Electromagnetic radiation (power lines, rail tracks, radio and TV-transmitters)
> Highways and major roads> Agricultural and other areas with high pesticide use (fruit
trees, grapes, golf courses)> Socio-economic status (area-based measure) > Average number of children per household (area-based
measure)> Degree of urbanization
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
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Adjusted results(for one confounder at a time)
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
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Power of CANUPIS
Beta= 76%Alpha=5%
2.2
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
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2.21.2
Power of CANUPIS
Beta= 76%Alpha=5%
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
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3% 2.21.2
Power of CANUPIS
Beta= 76%Alpha=5%
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
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IIIIIIIV
IIIIIIIV
IIIIIIIV
All cancers, age 0-15 years
NPPs
All nuclear installations
Planned NPPs
Poisson regression m
odel for children w
ith any cancer aged 0-15 years, 1985-2009
Presenter
Presentation Notes
The study was criticised for - potential selection bias, because communities in the vicinity of NPPs did not cooperate well For lack of adjustment for confounders And for looking only at residence at diagnosis. Considering that there is a lag time of several years between exposure to ionising radiation and development of cancer, residence prior to diagnosis, particularly during the intrauterine development and the first year of life, would be more informative.
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Conclusions
> No evidence for an increased risk of leukemia or all cancers in the vicinity of NPPs or all nuclear installations in Switzerland, 1985-2009
> No dose-response relationship, differences between observed and expected numbers of cases likely to be due to the play of chance
> Results consistent in a large number of additional and sensitivity analyses
> Small number of cases leads to statistical uncertainty
Presenter
Presentation Notes
Caused by worries of the Swiss population and parliament, the Swiss Federal Office of Health and the Swiss Cancer league asked the SCCR to investigate the situation in Switzerland. We aimed to overcome limitations of previous studies: Choosing a national cohort study design, including as baseline population all children living in Switzerland. These data came from the Swiss National cohort and census datasets, over 1.3 million children or 31 million person-years. Incident cases diagnosed since 1985 were identified from the SCCR. For geocoding we used exact addresses, not only information on the midpoint of the community where the children lived We focused on residence at birth rather than at diagnosis And, last, we adjusted for potential confounders, exposures that are more common in proximity to NPPS and cause cancer by themselves, such as natural radiation, power lines, roads or socio-economic status.
Thanks
> Funders: Bundesamt für Gesundheit (BAG), Krebsliga Schweiz (KLS)> Research team: Ben Spycher, Martin Feller, Aysel Güler, Marcel Zwahlen
(Bern); Martin Röösli (Basel); Heinz Hengartner (St. Gallen); Nicolas von der Weid (Lausanne)
> Scientific Advisory Committee: Maria Blettner (Mainz); François Bochud (Lausanne); Paolo Boffetta (Lyon); Sander Greenland (Los Angeles); Andreas Hirt (Bern); Charles Stiller (Oxford); Jan Vandenbroucke (Leiden).
> Swiss Pediatric Oncology Group (SPOG): R. Angst (Aarau); M. Paulussen & T. Kühne (Basel); P. Brazzola (Bellinzona); A. Hirt & K. Leibundgut (Bern); A. H. Ozsahin (Genf); B Popovic (Lausanne); L. Nobile Buetti (Locarno); J. Rischewski & U. Caflisch (Luzern); J. Greiner (St. Gallen); M. Grotzer & F. Niggli (Zürich)
> Swiss National Cohort: F. Gutzwiller, M. Bopp, D. Faeh (Zürich,); K. Clough-Gorr, K. Schmidlin, A. Spoerri, M. Sturdy (Bern); N. Künzli (Basel); F. Paccaud (Lausanne); M. Oris (Genf)
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