Cancer Causes Control (2014) 25:171–177 DOI 10.1007/s10552-013-0319-5

ORIGINAL PAPER

Distance from residence to power line and risk of childhood leukemia: a population-based case–control study in Denmark Camilla Pedersen • Ole Raaschou-Nielsen • Naja Hulvej Rod • Patrizia Frei • Aslak Harbo Poulsen Christoffer Johansen • Joachim Schu¨z



Received: 10 October 2012 / Accepted: 24 October 2013 / Published online: 7 November 2013 Ó Springer Science+Business Media Dordrecht 2013

Abstract Purpose Epidemiological studies have found an association between exposure to extremely low-frequency magnetic fields (ELF-MF) and childhood leukemia. In 2005, a large British study showed an association between proximity of residence to high-voltage power lines and the risk of childhood leukemia. The association extended beyond distances at which the ‘power line’-induced magnetic fields exceed background levels, suggesting that the association was not explained by the magnetic field, but might be due to chance, bias, or other risk factors associated with proximity to power lines. Our aim was to conduct a comparable study in an independent setting (Denmark). Methods We included 1,698 cases aged \15, diagnosed with leukemia during 1968–2006, from the Danish Cancer Registry and 3,396 controls randomly selected from the Danish childhood population and individually matched by gender and year of birth. We used geographical information systems to determine the distance between residence at birth and the nearest 132–400 kV overhead power line.

Results Odds ratios (ORs) were 0.76 [95 % confidence interval (CI) 0.40–1.45] for children who lived 0–199 m from the nearest power line and 0.92 (95 % CI 0.67–1.25) for those who lived 200–599 m away when compared with children who lived C600 m away. When restricting the analysis to 220 and 400 kV overhead power lines, the OR for children who lived 200–599 m from a power line was 1.76 (95 % CI 0.82–3.77) compared to children who lived C600 m away. However, chance is a likely explanation for this finding as the result was not significant, numbers were small, and there were no indications of an higher risk closer to the lines since no cases were observed within 200 m of these. Conclusions We found no higher risk of leukemia for children living 0–199 m or for children living 200–599 m of a 132–400 kV overhead power line. A slightly elevated OR for children living between 200 and 599 m of a 220–400 kV overhead power line is likely to be a chance finding. Keywords Childhood leukemia  Power lines  Electromagnetic fields  Case–control study

C. Pedersen (&)  O. Raaschou-Nielsen  P. Frei  A. H. Poulsen  C. Johansen Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen Ø, Denmark e-mail: [email protected] N. H. Rod Social Medicine Section, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark J. Schu¨z Section of Environment and Radiation, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France

Introduction Since Wertheimer and Leeper in 1979 [1] found an association between residential exposure to ELF-MF and childhood leukemia risk, several epidemiological studies have been conducted in this field. In 2000, two pooled analysis were published [2, 3], reaching similar conclusions of a higher risk of childhood leukemia associated with exposure to ELF-MF above 0.3/0.4 lT. In 2001, a working group at the International Agency for Research on Cancer (IARC) classified exposure to ELF-MF as ‘possibly

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carcinogenic to humans’ [4]. A recent pooled analysis of studies published after 2000 [5] found similar results to the two earlier pooled studies, though the association was weaker and not statistically significant. There is no obvious biological explanation for the association, and the epidemiological findings are not supported by animal studies [6]. Therefore, it is unknown whether the observed associations between ELF-MF and risk of leukemia in children indicate a causal relationship or are due to bias or confounding [6, 7]. In 2005, a large-scale case–control study conducted in Great Britain by Draper et al. [8] showed an association between proximity of residence at birth to high-voltage power lines and risk of childhood leukemia. The association extended ([200 m) beyond distances at which the ‘power line’-induced magnetic fields exceed domestic background levels [9, 10], suggesting that the association was not explained by the magnetic fields, but might be due to chance, bias, or other risk factors occurring more frequently near power lines. Even though controls in the study by Draper et al. were selected from registers and the potential for selection bias should be limited, the controls matched to the leukemia cases tended to live further from power lines than the controls matched to children with other cancers. Thus, the controls for the leukemia cases might by chance not have been representative of the relevant population, and the association might have been due to the controls living further away rather than to the leukemia cases living closer to power lines [8, 11]. Several studies investigated the association between residential proximity to power lines and the risk of childhood leukemia [12–19]; however, only few have investigated the risk in distances 200–599 m from power lines [17–19]. In a British study by the UK Childhood Cancer Study Investigators in 2000 [17], an OR of 0.75 (95 % CI 0.45–1.25) within 50 m of a power line was observed. Within 400 m of a 275–400 kV overhead power line, the OR was 1.42 (95 % CI 0.85–2.37), but because of different cut-off points, direct comparison with the Draper study is difficult. Sermage-Faure et al. [18] found an elevated (not statistically significant) risk of acute leukemia for children living within 50 m of an overhead power line with 225–400 kV (OR = 1.7 (95 % CI 0.9–3.6)), while the OR for 200–599 m was 1.2 (95 % CI 1.0–1.4). While SermageFaure et al. investigated distance from residence at diagnosis, Draper et al. looked at address at birth. A study from Brasil by Wunsch-Filho et al. [19] found a higher, though not statistically significant, risk of acute lymphocytic leukemia for children living within 200 m of a power line with 88–440 kV, whereas children living between 200 and 599 m showed no higher risk. While Wunsch-Filho et al. included power lines down to voltage with 88 kV, Draper

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et al. only looked at the higher voltage levels from 132 to 400 kV. A similar finding as the finding by Draper et al. would support the hypothesis that there might be a risk factor, independent of the magnetic field, associated with distance to power lines, whereas the opposite finding would support the assumption that the findings in study by Draper et al. might be due to chance or bias. Our aim was to investigate whether distance from residence at birth to the nearest power line is associated with a higher risk of childhood leukemia using nationwide data from Denmark, to conduct a comparable study to the study by Draper et al. in an independent setting. We also compared distance to the nearest power line with the estimated level of magnetic field at the residences.

Materials and methods Cases and controls We identified all children in Denmark diagnosed with leukemia before the age of 15 years during the period 1968–2006 (inclusive) from the virtually complete nationwide Danish Cancer Registry [20]. Children with a previous cancer diagnosis were excluded. Two controls for each case were individually matched by gender and year of birth and were selected by incidence density sampling from the Danish Central Population Registry. All children born in Denmark, who were alive, without cancer and living in Denmark at the time of diagnosis of their matched case were eligible to become a control in the study. We identified 1,698 cases diagnosed with leukemia during the period 1968–2006 and selected 3,396 matched controls (Fig. 1). Distance to nearest overhead power line The addresses of cases and controls at birth were obtained from the Danish Central Population Registry. We identified geographical coordinates by linkage to the Danish Address Database and collected data on existing and historical 132–400 kV overhead power lines with alternating current from the seven Danish transmission companies. The distance from residence at birth to the nearest power line that existed at the date of birth was calculated in ArcGIS 9.3. We successfully assigned geographical coordinates for addresses at birth and calculated the distance to the nearest power line for 1,577 cases (92.9 %) and 3,191 controls (94.0 %) (Fig. 1). For 121 (7.1 %) cases and 205 (6.0 %) controls, it was not possible to identify geographical coordinates for the address at birth, and therefore, distance to nearest power line could not be calculated. This was due

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Cases and controls for the period 1968-2006: Cases: 1698 Controls: 3396 Total: 5094

Number of cases and controls eligible for estimation of distance to nearest 132-400 kV overhead power line: Cases and controls in the period 1968-2006: Cases: 1698 Controls: 3396 Total: 5094

Distance to nearest 132400 kV overhead line could not be estimated: Cases:121 (7.1%) Controls:205 (6.0%) Total:326 (6.4%)

Number of cases and controls eligible for estimation of magnetic field strength: Cases and controls in the period 1968-2003: Cases: 1536 Controls: 3072 Total: 4608

Distance to nearest 132400 kV overhead line successfully estimated: Cases:1577 (92.9%) Controls:3191(94.0%) Total:4768 (93.6%)

Magnetic field strength successfully estimated: Cases:1474 (96.0%) Controls:2960 (96.3%) Total:4434 (96.2%)

Magnetic field strength could not be estimated: Cases:62 (4.0%) Controls:112 (3.6%) Total:174 (3.8%)

Number of cases and controls with both distance to nearest 132-400 kV overhead power line and magnetic field strength estimates: Cases:1415 Controls: 2867 Total: 4282

Fig. 1 Schematic presentation of for how many cases and controls distance and magnetic field strength was calculated

to either missing information (missing street name, postal district or house number) or historical addresses, which could not be identified in the Danish Address Database, which contains geographical coordinates for all addresses in Denmark in 2008. Draper et al. included mainly 275 and 400 kV lines and only a small fraction of 132 kV lines. Therefore, in addition to distance to nearest 132–400 kV power line, we calculated distance from residence to nearest 220–400 kV overhead power line, which was possible for 1,525 cases and 3,076 controls. There were 167 children who were born before the first overhead power line with 220–400 kV was put into operation, and therefore, distance could not be calculated for them. Estimation of exposure to magnetic fields from 50–400 kV facilities From a former Danish study of exposure to magnetic fields from 50–400 kV facilities and childhood cancer [13], we

had estimates of exposure to magnetic fields at address at birth for cases diagnosed in the period 1968–1986 and for their controls. Since then, magnetic field exposure has been estimated for cases diagnosed in the period 1987–2003 and their controls. Magnetic field strength at address at birth was successfully estimated for 1,474 (96.0 %) of the cases diagnosed with leukemia during the period 1968–2003 and for 2,960 (96.3 %) of their controls (Fig. 1). Magnetic field strength could not be estimated for 174 addresses owing to incomplete addresses. Addresses situated more than 150, 75, or 35 m from an overhead line or transformer substation with 220–400, 132–150, and 50–60 kV, respectively, and more than 20, 5, or 2.5 m from an underground cable with 220–400, 132–150, and 50–60 kV, respectively, were not considered to be exposed to a magnetic field from these installations. The distance criteria were used to identify addresses potentially exposed to magnetic fields of at least 0.1 lT, and for the addresses situated within these distance criteria, the magnetic field strength was estimated. In

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addition to distance, the estimation was based on the type of line, type of pylons (height of pylons, distance between pylons, and distance between phases), ordering of phases, current flow in the line, and date(s) of construction and any reconstructions. Further details of the calculations are given in a previous paper [13]. To validate the exposure assessment, magnetic fields were measured in six addresses close to 132 or 400 kV overhead lines, and the estimated field was close to the measured field with a correlation coefficient of 0.99. Additionally, six addresses far from high-voltage installations were chosen randomly. The average strength of magnetic field was 0.06 lT in the six addresses far from installations compared to an average field strength of 0.56 lT in the group close to installations. In the estimation of magnetic field strength, distance to 50–400 kV overhead lines, transformer stations and underground cables were used, whereas the distance calculation (described in the previous paragraph) used to conduct a comparable study to the study by Draper et al. was based on distance to the nearest 132–400 kV and distance to nearest 220–400 kV overhead lines, to replicate the study as close as possible. Socioeconomic status We adjusted for socioeconomic status of the municipality (categorical; \10, 10–90, [90 %), which was defined as the average gross income of the municipality for each year in the period 1976–1995 and is further described in a previous paper [21]. Children born during the period 1996–2006 were assigned the municipality income level based on data for 1995, and children born during the period 1953–1975 were assigned the level based on data for 1976. Statistical analysis Distance was categorized into three groups: 0–199, 200–599, and C600 m, corresponding to the categorization used by Draper et al. [8]. The association between distance and childhood leukemia was analyzed with conditional logistic regression models (PROC PHREG in SAS 9.2), providing ORs and 95 % CIs. We estimated the crude association as well as the association with adjustment for socioeconomic status of the municipality to follow the method of Draper et al. [8]. Further, we tested (likelihood ratio test) whether distance to the nearest 132–400 kV overhead power line (as a continuous variable) was associated with risk of childhood leukemia with a restricted cubic spline function. In a sensitivity analysis, we excluded 132 and 150 kV power lines and calculated the risk of childhood leukemia when living within 600 m of a power line with 220–400 kV.

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Results Most of the addresses at birth (94.9 %) were located 600 m or more from the nearest 132–400 kV overhead power line (Table 1). We did not find a higher risk of leukemia among children living close to a 132–400 kV power line at birth (Table 1). In comparison with children who lived 600 m or more from the nearest 132–400 kV power line, the OR was 0.76 (95 % CI 0.40–1.45) for those who lived 0–199 m from the nearest power line and 0.92 (95 % CI 0.67–1.25) for those who lived 200–599 m from the nearest power line after adjustment for socioeconomic status of the municipality. The results of the crude (unadjusted) analysis were virtually the same. The restricted cubic spline analysis showed no association between distance (as a continuous variable) and the risk of childhood leukemia (p = 0.55). No cases and only two controls lived within 50 m of a power line; therefore, the OR for this group could not be calculated. When restricting the analysis to overhead power lines with 220–400 kV, 27 children (14 controls and 13 cases) lived within 600 m of such a line. The OR was 1.24 (0.61–2.50) for those who lived within 600 m of a 220–400 kV power line compared to those who lived 600 m or more from the nearest line. Only six children were living within 200 m of a power line with 220–400 kV, and they were all controls. The OR for children living between 200 and 599 m from a 220–400 kV power line was 1.76 (0.82–3.77) (Table 2). Of the 4,282 addresses at birth, for which both distance to the nearest 132–400 kV overhead power line had been calculated and the magnetic field strength estimated (Fig. 1), 12 addresses were exposed to C0.1 lT (Table 3). Of the 12 addresses, five were situated 600 m or more from the nearest 132–400 kV overhead power line; three were due to power lines or cables with 50–60 kV; and two were close to historical 132–150 kV lines, for which we had no information for the distance calculation. Of the 4,270 addresses exposed to \0.1 lT, 36 were situated 0–199 m away from 132 to 400 kV overhead power lines.

Discussion Overall distance to nearest power line was not associated with a higher risk of childhood leukemia. We did not observe any association with close distance or further away. The primary analyses include power lines with voltage levels between 132 and 400 kV. When restricting the analysis to 220 and 400 kV power lines, no cases but six controls lived closer than 200 m to the line and the OR for children living between 200 and 599 m away was 1.76 (95 % CI 0.82–3.77).

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Table 1 Distribution of cases and controls and risk of leukemia by distance from address at birth to the nearest 132–400 kV overhead power line Distance (m)

Cases N (%)

Controls N (%)

Total N (%)

OR (95 % CI)

OR (95 % CI)a 0.76 (0.40–1.45)

0–199

13 (0.8)

34 (1.1)

47 (1.0)

0.76 (0.40–1.45)

200–599

62 (3.9)

135 (4.2)

197 (4.1)

0.90 (0.66–1.22)

0.92 (0.67–1.25)

1.00

1.00

C600

1,502 (95.2)

3,022 (94.7)

4,524 (94.9)

Total

1,577 (100.0)

3,191 (100.0)

4,768 (100.0)

a

Adjusted for socioeconomic status of municipality

Table 2 Distribution of cases and controls and risk of leukemia by distance from address at birth to the nearest 220–400 kV overhead power line Distance (m)

Cases N (%)

0–199

Controls N (%)

0 (0.0)

Total N (%)

6 (0.2)

6 (0.1)

200–599 C600

13 (0.9) 1,512 (99.2)

14 (0.5) 3,056 (99.4)

27 (0.6) 4,568 (99.3)

Total

1,525 (100.0)

3,076 (100.0)

4,601 (100.0)

a

OR (95 % CI)

OR (95 % CI)a





1.77 (0.83–3.77) 1.00

1.76 (0.82–3.77) 1.00

Adjusted for socioeconomic status of municipality

Table 3 Distance between residence and 132–400 kV overhead power lines and estimated magnetic fields at residence Distance (m)

0–199 200–599

Magnetic fields estimates (lT) C0.4

0.2–\0.4

0.1–\0.2

3 0

2 0

2 0

Total \0.1 36 179

43 179

C600

2

1

2

4,055

4,060

Total

5

3

4

4,270

4,282

Estimation of magnetic fields includes the following sources: 50–400 kV overhead lines, transformer substations, or underground cables

Five addresses far away from high-voltage power lines had elevated magnetic fields due to exposure to other sources than those used in the distance calculations, such as underground cables, transformer stations, 50–60 kV installations, and a few unidentified historical lines. In addition, 36 addresses were situated between 0 and 199 m from the nearest 132–400 kV overhead line but did not have a magnetic field higher than the domestic background level of the general population. Strengths and limitations Our study was a registry-based case–control study covering the entire population of Denmark over almost 40 years. Cases were drawn from a complete national cancer registry, and the Central Population Registry provided an excellent basis for limiting bias in sampling of controls. Also, the vast majority of addresses at birth were identified, allowing reliable calculation of distance between residence and power lines. The magnetic field exposure was calculated on basis of a number of relevant parameters and done

by experts in the utility industry without knowledge of the case–control status. As stated earlier, it was not possible to calculate an OR for children living within 50 m of an overhead power line with 132–400 kV and neither for children living within 200 m of an overhead power line with 220–400 kV due to few children living within these distances. Our study had limited statistical power; however, we included all cases with childhood leukemia in Denmark, and therefore, we maximized the potential in a Danish setting. Albeit a lack of statistical power to study very close proximity numbers were informative for greater distances, which are especially relevant for the open question of a higher risk in distances of 200–599 m as observed in the study by Draper et al. [8].

Comparison with other studies and interpretation The finding of no association between distance to nearest 132–400 kV overhead power line and childhood leukemia is in contrast to the finding in a British case–control study by Draper et al. in 2005 [8]. While we found an OR of 0.76 (95 % CI 0.40–1.45) among children who lived between 0 and 199 m compared to those who lived 600 m or more away from the nearest overhead power line, Draper et al. found a relative risk of 1.69 (95 % CI 1.13–2.53). Also, our finding of an OR of 0.92 (95 % CI 0.67–1.25) among children who lived 200–599 m of a line compared to those who lived 600 m or more away was in contrast to the finding by Draper et al. with a relative risk of 1.23 (95 % CI 1.02–1.49), although the risk of 1.23 was within our 95 % CI. The study by Draper et al. and our study estimated the distance from address at birth, were registry-based, and

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included power lines at the higher voltage levels. While we included power lines of 132–400 kV, Draper et al. included 275 and 400 kV lines and only a small fraction of the 132 kV lines. When we restricted our analysis to overhead power lines with 220–400 kV, we found an OR of 1.76 for children living 200–599 m of a power line with 220 or 400 kV. Although this result from an exploratory analysis appears to be in line with the findings by Draper et al., the estimate was not statistically significant, numbers were small, and we did not find an increased risk of closer distances (the six children living within 200 m were all controls) so chance must be considered a likely explanation and overall the two studies remain inconsistent. Our finding of no higher risk for children living within 200 m of power lines is in contrast to studies finding an association between ELF-MF exposure and childhood leukemia [2, 3]. The comparison between distance to 132–400 kV overhead power lines and magnetic field estimates revealed that including only 132–400 kV overhead lines, basing the calculations on distance without considering other factors such as power load and categorizing distance in 0–199, 200–599, and C600 m from the nearest power line gives rise to exposure misclassification if this method is used as a proxy for magnetic field exposure. In other studies, it has been demonstrated that distance from power lines alone is a poor proxy for exposure to magnetic fields and leads to misclassification [10, 22]. Therefore, this could be the reason for the difference between our findings and the studies investigating the risk associated with magnetic fields. Studies investigating the association between residential distance to high-voltage facilities and risk of childhood leukemia have found mixed results, and most studies have investigated close proximity (\200 m). Some studies have found an elevated though not statistically significant risk of leukemia associated with close proximity to power lines [12, 15, 18, 19], and other studies found no association with close proximity [13, 14, 16, 17]. Two recent studies [18, 19] have also investigated the risk in distances further from power lines: Sermage-Faure et al. [18] found an OR of 1.2 (95 % CI 1.0–1.4) for children living 200–599 m of a line with 225–400 kV, and Wunsch-Filho et al. [19] found that children living 200–599 m of a power line with 88–440 kV had no higher risk than children living further away. Even though the main focus of a British study conducted by the UK Childhood Cancer Study Investigators in 2000 was the risk associated with close proximity (\50 m) of a power line, they conducted an additional analysis to investigate the risk within 400 m of a 275–400 kV overhead power line and found an OR of 1.42 (95 % CI 0.85–2.37) for acute lymphocytic leukemia. If the OR of 1.76 (95 % CI 0.82–3.77) we observed for children living 200–599 m from a 220–400 kV overhead

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power line reflects a true elevated risk, it would suggest that a third factor is playing a role, as it was suggested on basis of the Draper et al’s finding. Our results would, however, suggest that such a factor only would be relevant in distance 200–599 m of a line and only for overhead power lines with very high voltage (220–400 kV). As we find it difficult to conceive of plausible factors fulfilling these criteria and given the small number and lack of significance, chance must be considered the most likely explanation. In conclusion, we found no higher risk of leukemia when living 0–199 m of a 132–400 kV overhead power lines at birth or when living 200–599 m away. A slightly elevated OR for children living between 200 and 599 m of a 220–400 kV overhead power line is likely to be a chance finding, and looking at the totality of our findings, we do not confirm the results of a previous large study using the same approach in Great Britain by Draper et al. Acknowledgments This work was supported by a grant by the foundation Children with Cancer UK (formerly Children with Leukemia), by Danish Energy for provision and estimation of exposure data; and by the Danish Cancer Society. Conflict of interest of interest.

The authors declare that they have no conflict

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Distance from residence to power line and risk of childhood leukemia: a population-based case-control study in Denmark.

Epidemiological studies have found an association between exposure to extremely low-frequency magnetic fields (ELF-MF) and childhood leukemia. In 2005...
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