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***Below are two letters published in the current August issue of Environmental Health Perspectives referencing an article published in January written by the CDC that reviewed the risk factors for acute leukemia in children. Here is the link to the original article, and the two letters follow in this e-mail back to back. Please note the retraction on benzene also in the review of risk factors. jill
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| http://www.ehponline.org/docs/2007/10217/letter.html |
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EMFs and Childhood Leukemia
Environ Health Perspect 115:A395-A399 (2007). doi:10.1289/ehp.10217 available via http://dx.doi.org [Online 24 June 2007]
Referencing: Risk Factors for Acute Leukemia in Children: A Review
In their otherwise informative and concise review of the current state of evidence concerning risk factors for acute childhood leukemia, Belson et al. (2007) did not correctly address nonionizing radiation and, in particular, power frequency magnetic fields as a possible risk factor for childhood leukemia. This failure may be due to a widespread misconception about the evidence concerning nonionizing electromagnetic fields (EMFs) as a health hazard. It is also apparent in the Churchill County leukemia cluster study published in the same issue, in which Rubin et al. (2007) investigated a multitude of factors, many with sparse or ambiguous previous evidence of an association with childhood leukemia. Although power frequency magnetic fields have been classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer (IARC 2002) and by a National Institute of Environmental Health Sciences (NIEHS) working group (NIEHS 1998), based on the evidence of an association with childhood leukemia, these were apparently not considered by Rubin et al. (2007).
In their review of nonionizing radiation, Belson et al. (2007) inappropriately mixed original research and pooled analyses, further contributing to the prevailing confusion. Both Ahlbom et al. (2000) and Greenland et al. (2000) presented pooled analyses that included the important study of Linet et al. (1997). Hence, it is inappropriate to present results of the latter as an independent source. Almost all epidemiologic studies of residential exposure to power frequency magnetic fields published before 1999 are included in either the pooled analyses of Ahlbom et al. (2000) or Greenland et al. (2000). Only the study of Myers et al. (1990) was not included because authors refused to provide requested data. Although the study of Linet et al. (1997) is often cited as failing to support the hypothesis of an association between residential exposure to magnetic fields and childhood leukemia [it was also cited by Belson et al. (2007)], it actually was one of the most important supporters of an association in the pooled analyses and contributed the greatest number of highly exposed children. Two large and well-conducted studies published after the pooled analyses (Kabuto et al. 2006; Schüz et al. 2001) lend further support to the results of the pooled analyses of an increased risk from high average levels of magnetic field exposure.
It is also incorrect to characterize the evidence as "some have found a small association . . . while others have not . . . ." First of all, the association is not small, but is comparable or larger than that for all other factors considered by Belson et al. (2007). Second, the evidence is consistent across different continents, study types, measurement methods, and other factors. Of course, there are potential sources of bias, in particular selection bias. However, thorough investigations of these potential biases have rendered it unlikely that they can completely explain the association. Up to now, there is no other risk factor of childhood leukemia that has been as comprehensively studied concerning possible biases and confounding factors.
It is high time that exposure to power frequency EMFs is recognized as a potential risk factor for childhood leukemia and is properly included in the protocols of cluster studies and in epidemiologic studies of other risk factors as a potential confounder.
The author declares he has no competing financial interests.
Michael Kundi
Institute of Environmental Health
Center for Public Health
Medical University of Vienna
Vienna, Austria
References
Ahlbom A, Day N, Feychting M, Roman E, Skinner, J, Dockerty J, et al. 2000. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 83: 692–698.
Belson M, Kingsley B, Holmes A. 2007. Risk factors for acute leukemia in children: a review. Environ Health Perspect 115:138–145; doi:10.1289/ehp.9023 [Online 30 November 2006].
Greenland S, Sheppard AR, Kaune WT, Poole C, Kelsh MA. 2000. A pooled analysis of magnetic fields, wire codes, and childhood leukemia, Childhood-EMF Study Group. Epidemiology 11:624–634.
IARC (International Agency for Research on Cancer). 2002. Non-ionizing radiation, part 1: Static and extremely low-frequency (ELF) electric and magnetic fields. IARC Monogr Eval Carcinog Risks Hum 80:1–395.
Kabuto M, Nitta H, Yamamoto S, Yamaguchi N, Akiba S, Honda Y, et al. 2006. Childhood leukemia and magnetic fields in Japan: a case-control study of childhood leukemia and residential power-frequency magnetic fields in Japan. Int J Cancer 119: 643–650.
Linet MS, Hatch EE, Kleinerman RA, Robison LL, Kaune WT, Friedman DR, et al. 1997. Residential exposure to magnetic fields and acute lymphoblastic leukemia in children. N Engl J Med 337:1–7.
Myers A, Clayden A, Cartwright RA, Cartwright SC. 1990. Childhood cancer and overhead powerlines: a case-control study. Br J Cancer 62:1008–1014.
NIEHS. 1998. Assessment of Health Effects from Exposure to Power-Line Frequency Electric and Magnetic Fields (Portier C, Wolfe M, eds). NIH publication no. 98-3981. Available: http://www.niehs.nih.gov/emfrapid/html/WGReport/WorkingGroup.html [accessed 9 July 2007].
Rubin CS, Holmes AK, Belson MG, Jones RL, Flanders WD, Kieszak SM, et al. 2007. Investigating childhood leukemia in Churchill County, Nevada. Environ Health Perspect 115:151–157; doi:10.1289/ehp.9022 [Online 30 November 2006].
Schüz J, Grigat J-P, Brinkmann K, Michaelis J. 2001. Residential magnetic fields as a risk factor for childhood acute leukaemia: results from a German population-based case-control study. Int J Cancer 91: 728–735.
Editor's note: In accordance with journal policy, Belson et al. were asked whether they wanted to respond to this letter, but they chose not to do so.
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Ionizing Radiation and Childhood Leukemia
Environ Health Perspect 115:395-399 (2007). doi:10.1289/ehp.10080 available via http://dx.doi.org [Online 24 June 2007]
Referencing: Risk Factors for Acute Leukemia in Children: A Review
I read with interest the recent review by Belson et al. (2007) on childhood leukemia, particularly the sections dealing with radiation exposure. Like the authors, I believe that ionizing radiation is strongly associated with childhood acute leukemia. I would like to point out that several critical pieces of information were overlooked; these support stronger and more meaningful conclusions.
Although atomic bomb survivors offer the clearest evidence of leukemia risk after childhood exposures to ionizing radiation, studies of children exposed to fallout in other contexts should not be downplayed. Belson et al. (2007) stated that "radiation exposure secondary to the Chernobyl accident has not been shown to increase the risk of leukemia in children who were exposed after birth . . . ," but they failed to mention the case–control study of Noshchenko et al. (2002), which found significant increases in childhood and acute leukemias in association with estimated childhood exposures. Children living downwind of the Nevada Test Site have also shown a significant increase in leukemia related to estimated fallout exposure (Stevens et al. 1990).
In utero exposure to ionizing radiation has been a known causal factor for childhood cancer for > 50 years. Although Belson et al. (2007) stated that the lack of evidence for a childhood leukemia risk among atomic bomb survivors constitutes the "most notable reason for doubt of a true association," they overlooked the reviews of Wakeford and Little (2002, 2003); these authors demonstrated that the highly uncertain atomic bomb survivor data are statistically compatible with the robust set of data found in the Oxford Survey of Childhood Cancers and related X-ray exposure cohorts. There is no valid reason to doubt this association at present.
The association between preconception paternal irradiation (PPI) and childhood leukemia has always been controversial. Two of the major objections to the "Gardner hypothesis," as Belson et al. (2007) pointed out, have been mixed evidence from studies of radiation-exposed fathers and a lack of positive evidence in the children of the atomic bomb survivors. Regarding the first objection, Belson et al. overlooked the two largest studies of the children of radiation workers. Draper et al. (1997) conducted a UK-wide case–control study of childhood cancers in relation to paternal radiation exposure. This study showed, based on > 13,000 cases not included in the study of Gardner et al. (1990), that children with leukemia or non-Hodgkin lymphoma were significantly more likely than controls to have fathers who were radiation workers. Dickinson and Parker (2002) conducted a cohort study of > 250,000 births in Cumbria, England, including the cases of Gardner et al. (1990), and found a significant 2-fold increase in the risk of leukemia and non-Hodgkin lymphoma among the children of radiation workers. These and other studies, taken together, give statistical support to the idea that paternal radiation work is a risk factor for childhood leukemia.
When interpreting the evidence for a PPI effect in atomic bomb survivors, it is important to consider what is known about potential mechanisms. As reviewed by Niwa (2003), Nomura (2003), and others, animal studies have consistently demonstrated that PPI can cause or increase the susceptibility to leukemia in offspring. In addition to fascinating evidence of postconception genomic instability after preconception exposure, many studies suggest that there may a window of sensitivity corresponding to postmeiotic stages of spermatogenesis; in humans, this would mean the few months leading up to conception (Adler 1996). Of the roughly 30,000 children of atomic bomb survivors, only about 2% were conceived in the 6 months after the bombings. Based on the spontaneous leukemia rate reported by Yoshimoto (1990), the expected number of spontaneous cases in this subcohort would be < 1, and an excess on the order suggested by the radiation worker studies would not be statistically apparent. For this and other reasons, the atomic bomb survivors may not be an appropriate comparison group.
To summarize, it is not unreasonable to observe that the weight of evidence generated to date supports the idea that preconception, prenatal, and postnatal exposures to ionizing radiation are all risk factors for childhood leukemia.
The author declares he has no competing financial interests.
Abel Russ
George Perkins Marsh Institute
Worcester, Massachusetts
References
Adler ID. 1996. Comparison of the duration of spermatogenesis between male rodents and humans. Mutat Res 352(1-2):169–172.
Belson M, Kingsley B, Holmes A. 2007. Risk factors for acute leukemia in children: a review. Environ Health Perspect 115:138–145.
Dickinson HO, Parker L. 2002. Leukemia and non-Hodgkin's lymphoma in children of male Sellafield radiation workers. Int J Cancer 99:437–444.
Draper GJ, Little MP, Sorahan T, Kinlen LJ, Bunch KJ, Conquest AJ, et al. 1997. Cancer in the offspring of radiation workers: a record linkage study. BMJ 315(7117): 1181–1188.
Gardner MJ, Snee MP, Hall AJ, Powell CA, Downes S, Terrell JD. 1990. Results of case-control study of leukemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ 300:423–429.
Niwa O. 2003. Induced genomic instability in irradiated germ cells and in the offspring: reconciling discrepancies among the human and animal studies. Oncogene 22: 7078–7086.
Nomura T. 2003. Transgenerational carcinogenesis: induction and transmission of genetic alterations and mechanisms of carcinogenesis. Mutat Res 544(2-3):425–432.
Noshchenko AG, Zamostyan PV, Bondar OY, Drozdova VD. 2002. Radiation-induced leukemia risk among those aged 0-20 at the time of the Chernobyl accident: a case-control study in the Ukraine. Int J Cancer 99(4):609–618.
Stevens W, Thomas DC, Lyon JL, Till JE, Kerber RA, Simon SL, et al. 1990. Leukemia in Utah and radioactive fallout from the Nevada test site. A case-control study. JAMA 264(5):585–591.
Wakeford R, Little MP. 2002. Childhood cancer after low-level intrauterine exposure to radiation. J Radiol Prot 22(3A):A123–A127.
Wakeford R, Little MP. 2003. Risk coefficients for childhood cancer after intrauterine irradiation: a review. Int J Radiat Biol 79(5):293–309.
Yoshimoto Y, Neel JV, Schull WJ, Kato H, Soda M, Eto R, et al. 1990. Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors. Am J Hum Genet 46(6):1041–1052.
Editor's note: In accordance with journal policy, Belson et al. were asked whether they wanted to respond to this letter, but they chose not to do so. | | | |
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