The epidemiological evidence on residential power-frequency magnetic fields and the risk for childhood leukemia

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1 Greeting アンニョンハシムニカおはようございます チョウムベッケッスムニダはじめまして チョヌンカブトラゴハムニダ私はカブトと申します アルゲテオキブムニダ知り合いになれてうれしいです テダニカムサハムニダどうもありがとうございます The 7th Korean EMF Workshop October 2003 The epidemiological evidence on residential power-frequency magnetic fields and the risk for childhood leukemia Michinori Kabuto ( 兜真徳 ) Acting Director for Health Reseach ( 首席研究官 ( 健康担当 )) National Institute for Environmental Studies ( 国立環境研究所 ) A WHO Collaborating Center for EMF 1

2 Backgrounds Previous risk evaluations for residential exposure to power frequency MF & childhood leukemia Rapid Program in the U.S. evaluated as possibly human carcinogenic (2B), 1998 Pooled analysis by Greenland, 2000 Pooled analysis by Ahlbom, 2000 IARC evaluated as possibly carcinogenic (2B), 2001 WHO International EMF Project ( ) recommended one or two epi studies to confirm An Epidemiologic Study on ELF-MF and Childhood Leukemia and Brain Tumor in Japan ( ) Principal Investigator: Michinori Kabuto Acting Director for Health Research, NIES A final report to MECSST was completed at May 2003 and uploaded on the website: ( in Japanese only) 2

3 Working members The Study Group Michinori Kabuto, DHSc (NIES) Hiroshi Nitta, DHSc (NIES) Seiichiro Yamamoto, Ph.D. (NCC) Naohito Yamaguchi, M.D. (NCC) Suminori Akiba, M.D. (Kagoshima U.) Yasushi Honda, M.D. (Tsukuba U.) Jun Hagihara, Ph.D. (Miyagi U) Katsuo Isaka, D.Eng. (Tokushima U.) Tomohiro Saito, M.D. (NICH) Toshiyuki Ojima, M.D. (Jichi Med. U.) Yosikazu Nakamura, M.D. (Jichi Med.U.) Tetsuya Mizoue, M.D. (UOEH) Akira Eboshida, M.D. (Hiroshima U.) Shin Yamazaki, M.P.H. (Kyoto U.) Shigeru Sokejima, M.D. (Kyoto U.) Yoshika Kurokawa, M.D. (NIES) Osami Kubo, M.D. (TWMC) Collaborative and supporting groups Participants families 5 Child Cancer (Leukemia) Research Groups MOES Research Promotion Committee (Chairperson: Dr. Fumimaro Takaku, Jichi Med. U.) Subjects and Methods 1. Childhood leukemia (interview) 2. Childhood leukemia (mail) 3. Childhood brain tumor (interview) 3

4 Basic points considered for the present study Power calculation indicates a need of 1,000 cases if RR is 1.5 but less if RR is larger Short interval between diagnosis and interview Study period of 3 years but 2.3 years for survey Size of the catchment area by home-visit interview Direct and 1 week measurements of MF for child s bedroom according to pilot study Matched for measuring time between case and controls to reduce errors due to possible seasonal variations Case Selection Newly diagnosed cases with age of below 15 years diagnosed during 2.3 years from Childhood cancer study groups 1) TCCSG 2) CCLSG 3) Tohoku Childhood Cancer Study Group 4) JACLS 5) Kyushu Childhood Cancer Study Group The central office in the NCC_RI: 1,606 were registered (from all Japan= 20 million children) This is roughly equal to 700 cases per year or 3.5 cases per 100,000 children = another estimate 4

5 Number of Subjects in the catchment area or 18 prefectures covering 53 % of the total population The catchment area for interview survey Control Selection Gender, age and population size were matched - 123,000 control candidates were randomly selected. multi-step random sampling with considering agedistribution of cases and population-size for each of the selected area -10 candidates were selected for each new case and requested for participation -home-visit interview survey 1 case vs. 1-3 controls 5

6 Cases and controls selection in the catchment area Cases requested through physisian791 Participants 391 (50 %) Majority of non-participants had not been requested by the physician C ontrols requested Participants 1 097(27%) Not studies or excluded 79 cases and 494controls 312 case-control sets 312 cases (251ALL,61AML) 603 controls(495all,108aml) due to: Mainly Time limit to continue the study For small number: Move after diagnosis Instrument failure Changed to mail survey Matched controls or cases were lost The subjects for risk analyses cases controls ALL 251 ( 80 %) 495 AML 61 ( 20 %) 108 Total 312 (100 %) 603 6

7 Home-visit interview The questionnaire based on the NCI study Demographic variables History of moves after pregnancy Resident type Mother s, father s and child s histories of use of insecticides, smoking, drinking, labor, hazardous chemicals, drugs, electric appliances Mother s history of clinical X-ray, spontaneous abortion etc. Measurements 1) 1week measurements (30 sec intervals) for child s bedroom (EMDEX-Lite, Enertech Co. Ltd.) 2) Point measurements for 5 min (EMDEX II, Enertech Co. Ltd.) Child s bedroom (center, at head when sleeping) room where child spend longest time daily 4 corners of house for detached house and front door and opposite window for apartment house 3) Distance to the nearest line of high voltage power line if it exist within 100 m by the Laser Distance Meter 4) Indoor γ-ray, benzene and radon 7

8 Methods of MF measurements for child s bedroom Instrument: EMDEX-Lite Set position: nearby the head of child during sleep where MF level was not affected by MF from appliances (so called as background MF level ) 20,160 measurements with 30 sec interval for a week Arithmetic mean level was used as the exposure surrogate period of inquiry birth Period of inquiry MF measure onset end diagnosis interview Pregnant period Length at the present house Exclude those who moved after diagnosis 8

9 Cases and Controls of Childhood Leukemia - Length of living in the residence when diagnosed- Case N % Control N % Residence type detached apartment % period of inquiry < length of living at present house < 12 months Results 9

10 Cases and Controls of Childhood Leukemia - Gender and age at diagnosis - Case N % Control N % Gender male female age at diagnosis 5 yrs Strength of the present study Registered almost all new cases New cases as fresh as possible 1.1 years on the average Survey was titled as living environment and child s health Home-visit interview 1 week MF measurement Case-control matched MF measurements 2.6 days on the average Indoor benzene measurements Indoor radon measurements Indoor radiation measurements 10

11 Childhood leukemia D istribution of bedroom M F levels A LL cases and controls only Bedroom M F level in m icro te sra micro tesra cases and controls control case 11

12 Risk of child s bedroom MF level for childhood leukemia (ALL+AML) Conditional logistic regression analyses Childhood leukemia (ALL+ AML) Child s bedroom MF level (μt) < above 0.4 Cases Control OR (95%CI) ( ) 1.09 ( ) 2.63 ( ) Risk of child s bedroom MF level for ALL alone Conditional logistic regression analysis ALL alone Child s bedroom MF level (μt) < above 0.4 Cases Controls OR (95%CI) ( ) 1.03 ( ) 4.73 ( ) 12

13 Hourly mean MF level,μ ALL cases(n=6) case1 case3 case5 case2 case4 case Sun M on Tue W ed Thu Fri Sat o'lock bedroom MF level 0.4 µt Hourly mean MF level,μ A LL controls (n=3) control1 control2 control Sun M on Tue W ed Thu Fri Sat o'lock Potential selection bias Sensitivity analyses difference in participation rate in relation to distance to power line Potential confounders RR changes when potential confounders were added as covariates in the conditional logistic model child s use of various electric appliances mother s use of various electric appliances mother s history of X-ray test, drugs, pesticides mother s history of education and occupation 13

14 Summary Major findings for childhood leukemia Risk of childhood leukemia of above 0.4 µt was 2.63 ( ) and that for ALL alone was 4.73 ( ). High exposure group of above 0.4 µt was less than 1 % as was reported for other coutries. High exposures were attributed to not only high voltage power line but also distribution lines (6.6 kv or 7.7 kv) with a few exceptions. A risk of electric blanket use by children was suggested. Bias and confounding effect by potential confounders were not suggested according to sensitivity analyses and mutiple conditional logistic regression analyses, respectively., so far conducted. 14

15 Pooled results by Ahlbom (2000) Exposure RR (95% CI) No. cases µt 1.08 ( ) µt 1.11 ( ) 104 <0.4 µt 2.00 ( ) 44 Epidemiological evidence of the risk of ELF for childhood cancer Anders Ahlbom Karolinska Institute, Sweden 15

16 Background First study on EMF and childhood cancer 1979 First study on EMF and adult cancer 1982 First study on occupational EMF and cancer 1982 Diseases Cancer Children Leukemia CNS Adults Leukemia CNS Breast cancer Other hormone dependent Myocardial infarction Neurodenerative Depression Suicide Hypersensitivity 16

17 Methods: exposure Wire codes Distance between home and power line Spot measurements Calculated fields 24/48-h measurements Methods: other aspects Confounding Selection bias Due to non-response Due to design features Evaluation of random variability 17

18 EMF and childhood leukemia Study RR 95 % C.I. Wertheimer & Leeper Fulton Tomenius Savitz Coleman Myers London Feychting Olsen Verkasalo Tynes Michaelis Linet Dockerty MacBride Green UKCCS TOTAL Childhood leukemia studies with 24/48 hour measurements or calculated fields 10 1 Pooled 0,1 18

19 Pooled analysis of childhood leukemia Recent 24/48 h. measurement studies Calculated field studies Primary data 9 studies N ca = 3,247; N co = 10,400 Ahlbom et al. BJC, 2000 Primary data: Improves compatibility Diagnostic categories Exposure definitions Exposure levels Allows analyses not done in single studies Higher cut off points 19

20 Research questions Association between EMF and childhood leukemia? If so, is this affected by adjustment for potential confounders? Is there evidence for the wire code paradox? Association between EMF and childhood leukemia? Is chance a likely explanation? Is selection bias a likely explanation? 20

21 Pooled results Exposure RR (95% CI) No. cases µt 1.08 ( ) µt 1.11 ( ) 104 <0.4 µt 2.00 ( ) 44 RR 95% C.I < < < µt 21

22 Conclusion The association seems to be too strong to be explained by chance Selection bias: Sensitivity analysis 0.4 µt All studies 2.0 ( ) US excluded 1.7 ( ) Canada excl. 2.1 ( ) 22

23 Selection bias: Stratified analysis 0.4 µt All studies 2.0 ( ) Nordic countries 2.1 ( ) Rest of the world 1.9 ( ) Conclusion Exclusion of studies prone to selection bias does not change results Comparing groups of studies with different proneness to selection bias reveals no difference Thus, no suggestion that selection bias explains the association 23

24 Greenland et al Original individual data from 12 studies 8 studies were included also in the previous meta-analysis Pooled analysis. Greenland, 2000 Greenland et al. Epidemiology

25 Doll report Recent studies have provided better evidence they suggest that exposures of 0.4 µt or more are associated with a doubling of the risk of leukemia in children The evidence is, however, not conclusive. IARC evaluation, June 2001 ELF magnetic fields are possibly carcinogenic to humans (2B) 25

26 Possible explanations for observed excess risk Systematic error Selection bias Measurement error Confounding Random error Causation Implication of IARC 2B classfication Scientific uncertainty From public health perspective, treat as if carcinogenic Further questions Risk function Public health impact Policy options 26

27 More research Japanese study UK study.. May help to increase Importance of systematic error Risk function Mechanisms What next? WHO is considering Preactionary Framework in relation to revising their environmental health criteria From do nothing to invoking some actions 27

28 テダニカムサハムニダどうもありがとうございます多謝!! Thank you very much 28