Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Early exposure to infection and childhood leukaemia
- Roger C Parslow, Richard G. Feltbower and Patricia A. McKinney. (22 April 2005)
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Vaccinations and immunity.
- Richard Lanigan (24 April 2005)
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Daycare and Leukaemia Greaves and/or Kinlen
- James E Parker (1 May 2005)
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Immune protection against leukaemia
- John M. Grange, Bernd Krone and Klaus Koelmel (3 May 2005)
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Prevention of childhood leukemia: Is it possible?
- Petar I. Ivanovski (5 May 2005)
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Day care in infancy and childhood leukemia
- Samuel Milham (13 May 2005)
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Re: Prevention of childhood leukemia: Is it possible?
- L. Travis Haws (14 May 2005)
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Immunization and Childhood Leukarmia
- Michael D Innis (26 May 2005)
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Re: Immunization and Childhood Leukarmia
- James E Parker (28 May 2005)
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Re: Re: Immunization and Childhood Leukaemia
- Michael D Innis (1 June 2005)
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Comment on Day Care Paper
- Maureen Asbury (12 June 2005)
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Comment on Gilham et al BMJ 22 April 2005
- Michael J O'Carroll (19 June 2005)
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Cortisol and Stress in Children
- Trevor S Parry (4 August 2005)
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Roger C Parslow, Senior Research Fellow Paediatric Epidemiology Group, University of Leeds, LS2 9LN, Richard G. Feltbower and Patricia A. McKinney.
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Gilham et al’s findings(1) are a significant contribution to the understanding of the aetiology of childhood leukaemia and support earlier research carried out in this field including a study based on the same UKCCS dataset examining population mixing as a proxy for infectious exposure and childhood cancer (2). This related study lends further weight to their findings as it uses a different and independent exposure metric but produces analogous results. Our group has also investigated the effect of early social contact in relation to childhood diabetes (3) and population mixing in relation to childhood cancer (4), and parallels between the two conditions which seem to share some aspects of a common aetiology.(5). All of these studies point to similar results. Exactly what type of infection or group of infections are important in improving immunological competence and the biological mechanisms by which these operate are yet to be established. Striking the right balance between protecting our children from damaging or life threatening infections whilst exposing them to a ‘sufficient dose’ of milder infections to prime their immune systems, has far-reaching social and behavioural connotations. 1 Gilham C, Peto J, Simpson J, Roman E, Eden TOB, Greaves MF, Alexander FE, for the UKCCS Investigators. Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study. BMJ, doi:10.1136/bmj.38428.521042.8F (published 22 April 2005) 2 Law GR, Parslow RC, Roman E. Childhood cancer and population mixing. Am J Epidemiol 2003;158:328-36 3 McKinney PA, Okasha M, Parslow RC, Law GR, Gurney KA, Williams DRR, Bodansky HJ. Early social mixing and childhood type 1 diabetes: a case- control study in Yorkshire, UK. Diabet Med 2000;17(1):236-242 4 Parslow RC, Law GR, Feltbower R, Kinsey SE, McKinney PA. Population mixing, childhood leukaemia, CNS tumours and other childhood cancers in Yorkshire. Eur J Cancer 2002; 38:2033–2040. 5 Feltbower RG, Manda SOM, Gilthorpe MS, Greaves MF, Parslow RC, Bodansky HJ, Kinsey SE, McKinney PA. Small area similarities in the epidemiology of childhood acute lymphoblastic leukaemia and Type 1 diabetes: a Bayesian approach. Am J Epidemiol 2005; In press. Competing interests: None declared |
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Richard Lanigan, Chiropractor The Park Clinic, Kingston, KT2 6DQ
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Gilham et al’s findings should not come as a surprise, however they have stopped short of questioning the possible benefits to the immune system of what were once called “normal childhood infections” and now, are extremly rare. Prevention of infectious diseases is seen universally as beneficial to the health of society. However few have considered the possibility that natural selection and these diseases, played a role in the development of the immune system to fight more deadly diseases. Alm, Swartz, Lilja, Scheynius and Pershagen (1999) found that children who took fewer antibiotics had a lower rate of immunisation and also had a lower prevalence of asthma , eczema and hay fever than the controls. Bodner, Anderson, Reid and Godden (2000) reported that children who contracted measles are less likely to go on and develop asthma, a disease that was rare thirty years ago and now kills 2000 people per year in the UK. Hurwitz and Morgenstern concluded that DPT vaccination increased the risk of allergy. Shaheen, Aaby and Hall (1996) found a specific inverse relationship between contracting measles and atopic diseases. Kemp, Pearce and Fitzharris (1997) found that a small sample of children who did not have DPT or polio immunisation did not suffer from asthma or other allergic illnesses compared with 23 per cent. of the main sample who suffered asthma episodes and 30 per cent. who suffered other allergic illnesses. Kramer, Heinrich, Wjst and Wichmann (1999) supported the hypothesis that early infection may protect against allergies later in life. Gibbon, Smith, Egger, Betts and Phillips (1997) found that children who suffered infections in the first year of life were less likely to develop insulin dependent diabetes. Classen and Classen (1999) found that immunised children had twice the incidence of diabetes type 1. There is no doubt that the introduction of mass vaccination programmes in Cuba after the revolution reduced the incidence of death from measles and other childhood diseases, at a time when sanitation, nutrition and housing was poor. Cuba now has achieved life expectancy and infant mortality rates similar to developed countries. However, it also has a high prevalence of asthma similar to North America and Europe (MacDonald,1999) and other autoimmune disorders. Alm, J S, Swartz, J, Lilja, G, Scheynius A, Pershagen G (1999), Atopy in children of families with an anthroposophic lifestyle, Lancet, 353,1485 -8 Bodner, C, Anderson, W J, Reid, T S and Godden, D J (2000), Childhood Exposure To Infection And Risk Of Adult Onset Wheeze And Atopy, Thorax, 55, 383-387 Gibbon, C, Smith, T, Egger, P, Betts, P and Phillips D (1997), Early infection and subsequent insulin dependent diabetes, Arch Dis Child, 77, 5, 384-5 Hurwitz E L and Morgenstern H, (2000), Effects of diphtheria-tetanus- pertussis or tetanus vaccination on allergies and allergy-related respiratory symptoms among children and adolescents in the United States, Journal of Manipulative and Physiological Therapeutics, 23(2), 81-90 Johnston, S. and Openshaw, P. (2001), The Protective Effect of Childhood Infections, BMJ, 322, 376-377 Kramer, U, Heinrich, J, Wjst, M and Wichmann, H E (1999), Age Of Entry To Day Nursey And Allergy In Later Childhood, Lancet, 353, 450-454 Macdonald, T H (1999), A Development Analysis Of Cuba’s Health Care System Since 1959, The Edwin Mellen Press Shaheen, S O, Aaby, P, Hall, A J, Barker, D J, Heyes, C B, Shiell, A W and Goudiaby A (1996), Measles and atopy in Guinea-Bissau, Lancet, 347, 1792-6 Competing interests: None declared |
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James E Parker, Retired Paediatrician 289 McCallum Rd Abbotsford BC CANADA V2S 8A1
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This is an important and significant paper. The implicit suggestion however that daycare in early infancy protects against the development of childhood acute lymphoblastic leukaemia (ALL) stretches the imagination just a little. On the other hand the paper delineates a population of 'protected' at risk children of (?) 'stay at home mothers'. It is presented as evidence of the role of nonspecific infection as a 'second hit' in the induction of disease in keeping with the hypothesis of Professor Mel Greaves. While endorsing the Greaves ' hypothesis, at first blush, this would appear to run counter to the suggestions of Kinlen regarding miniepidemics involving an (as yet) unknown agent generated by population mixing........And yet. Greaves prescient discovery, by the detection of disease markers on Guthrie cards, that childhood ALL was a disease of long latency is exciting. This reconciles with Jean Cooke's 1942 historic paper (JAMA 1942; 119:547-50) describing the 'childhood peak' which she eqated with infectious disease. A long period of leukaemic disease latency is described in another species (felix domestica) in which an exogenous horizontally transmitted retrovirus (FeLV) has been discovered. (A similar situation has been noted in cattle). Such an agent has not as yet been found in association with childhood ALL. If the 'first hit' occurs as Greaves suggests in utero at the materno/foetal level, this would appear to be a prime area of search for such an agent. James E Parker Competing interests: None declared |
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John M. Grange, Visiting professor Centre for Infectious Diseases and International Health, University College London, 46 Cleveland Str, Bernd Krone and Klaus Koelmel
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The study by Gilham et al. confirms the hypothesis that reduced exposure to infection early in life has effects on the maturing immune system that increase the risk of acute lymphoblastic leukaemia (ALL) and possibly other malignancies. The immunological basis of this increased risk is uncertain but it could be the result of the inadequate development of immune surveillance mechanisms that detect cancer-specific antigenic determinants. This suggestion raises the possibility of using vaccination strategies to replace the environmental contacts that would otherwise lead to immune maturation. Gilham et al. mention Haemophilus influenzae type b vaccination in this respect but another possible vaccine is Bacille Calmette Guerin (BCG) which, when given early in life, has been shown in several studies to afford protection against ALL.1 In this context, a working group of the European Organization for Research and Treatment of Cancer (EORTC) has shown that vaccination with BCG early in life, as well as vaccinia vaccination and certain serious but uncommon infections, reduces the risk of the subsequent development of melanoma by around 50% and that, in comparison with those not vaccinated, a history of one or other, or both, of these vaccinations is related to significant improvement in the survival time of those developing melanoma.2 Further investigations are required to confirm the protective effect of BCG against leukaemia and melanoma and to determine whether it protects against other cancers. If so, a re-introduction of this vaccine could have significant impacts on human health. Gilham et al. postulate that the inadequate priming of the immune system due to a lack of exposure to infection permits subsequent infections by unknown exogenous agents, probably viruses, to cause immune dysregulation leading to ALL. This may occur but an alternative possibility is that the causative agent is not an exogenous one but a human endogenous retrovirus (HERV). In the case of melanoma, we have suggested that a failure of immune surveillance permits expression of a member of the HERV-K family of endogenous retroviruses.3 This expression leads to intracellular changes resulting in malignant transformation and also to the presentation of an epitope, HERV-K-MEL, on the cell surface. Interestingly, BCG, vaccinia and the agents causing the protective infectious diseases contain homologs of the HERV-K-MEL epitope and could therefore afford protection by generating a population of cross-reacting memory T cells that are involved in immune surveillance of pre-malignant and malignant cells. If such HERV-related epitopes are involved in ALL and other cancers their identification could, perhaps, lead to the development of a vaccine affording protection against a range of cancers. John M.Grange
Bernd Krone
1. Grange JM, Stanford JL. BCG vaccination and cancer. Tubercle 1990; 71: 61-64. 2. Kölmel KF, Grange JM, Krone B, et al. Prior immunisation of patients with malignant melanoma with vaccinia or BCG is associated with better survival. An European Organization for Research and Treatment of Cancer cohort study on 542 patients. European Journal of Cancer 2005, 41: 118- 125. 3. Krone B, Kölmel KF, Henz BM, Grange JM. Protection against melanoma by vaccination with Bacille Calmette-Guérin (BCG) and/or vaccinia: an epidemiology-based hypothesis on the nature of a melanoma risk factor and its immunological control. European Journal of Cancer 2005, 41: 104-117. Competing interests: None declared |
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Petar I. Ivanovski, pediatrician University Childrens Hospital, Belgrade, 11000
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Speculating about the infective etiology of acute leukemia in children, in her fascinating paper from 1942 (1) Jean V. Cooke wrote: ‘…it occurs only in certain persons in whom a constitutional inferiority of the hematopoietic system makes it vulnerable to injury by infections and possibly by other types of trauma.’ Over half a century later, Greaves et al. deciphered the meaning of ‘the constitutional inferiority of the hematopoietic system’ (2). Thus, owing to his ingenious project, today we know that most of childhood leukemias have prenatal origin. Leukemogenic translocations originating during fetal life are insufficient for overt leukemia. This has been additionally confirmed by experiments with transgenic TEL-AML1 mice, which failed to develop leukemia (3). Thus, it has been concluded that additional mutations or abnormal expression of another gen(s) may be necessary to promote leukemogenesis, perhaps through increased proliferation. According to Gilham et al’s findings (4) and Greaves’ hypothesis (5), leukemia occurs in children who lack early immunomodulation, and who later contract some common infection of low pathogenicity. Having in mind a very stable incidence of childhood leukemia and the need of multiple very regular proliferative stresses on B cell precursors with TEL-AML1 fusion to cause additional mutations (allelic TEL deletions) for overt leukemia, naturally we must ask the question: Which is the infection of low pathogenicity that is capable of causing a proliferative stress, and at the same time to be repetitive and to occur every year so as to lead to a stable incidence of leukemia? Before 1920, acute leukemia among children was a rare event. A significant peak-age incidence (2-5 years) appeared after 1940 (6). Since then, the incidence rate of childhood leukemia has been more or less remarkably stable (7). This means that some leukemogenic factor must have been introduced in children's lives some time around 1940 (6). It is a highly striking coincidence that at the same year the introduction of immunization against diphtheria was began on a national scale (8). Further experimental work on transgenic TEL-AML1 mice, exposed to diphtheric anatoxin should be conducted to investigate if there is any relationship between the introduction of systemic vaccination against diphtheria and the peak age incidence (at age 2-5 years) appearance of childhood leukemia. If some of these mice develop leukemia, we shall make a great step toward the prevention of childhood leukemia. This would then call not for rejection, but for a future redefinition of vaccination schedule (9). 1.Cooke JV, (1942) JAMA 119:547-50. 2.Greaves MF, (1999) Lancet 354:1499-03. 3.Andreasson P, (2001) Cancer Genet Cytogenet 130: 93-104. 4.Gilham C, (2005) BMJ April 22. 5.Greaves MF, (1997) Lancet 349:344-49. 6.Court Brown, WM, (1961) Br Med J 1:981-8. 7.Hjalgrim LL, (2003) J Natl Cancer Inst 95:1539-44. 8.Salisbury DM, Begg NT. Immunisation Against Infectious Disease. HMSO, Department of Health, London, 1966, p.67. 9.Barrios C, (1996). Eur. J. Immunol. (July) 26 (7): 1489-96. Competing interests: None declared |
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Samuel Milham, physician/epidemiologist 2318 Gravelly Beach Loop NW, Olympia WA 98502
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Editor: The recently published study, Day care in infancy and the risk of childhood acute lymphoblastic leukaemia: findings from the UK case -control study by Gilham et al(1), has a major problem with bias created by selective non-response in the control group. Figure 3 of the United Kingdom Childhood Cancer Study (UKCCS): objectives, materials and methods(2) shows that of 11,987 eligible controls, only 7,629 (64%) of control parents were interviewed. A study linking the UKCCS study cases and controls to the 1991 census of Great Britain(3) showed that case families lived in more affluent areas than did first choice control families, but that compared with participating control families, the case families tended to live in areas that were less affluent than those of control families. Table 4 of the UKCCS study shows that 57.6% of case mothers were not gainfully employed compared to 47.3% of the participating control mothers. I suspect that since a larger proportion of participating control mothers were gainfully employed than were the case mothers, their use of day care would be higher. This is reflected in table 2 of the Gilham et al paper. I, therefore, think that the low calculated odds ratios of childhood leukemia in children attending day care in infancy is more likely to be due to a selection bias in control participation than to exposure to infectious agents in day care. REFERENCES 1. Gilham C, Peto J, Simpson J, Roman E, Eden TOB, Greaves MF, Alexander FE. Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from the UK case-control study. BMJ, doi:10.1136/bmj.38428.521042.8F (published 22 April 2005) 2. UK Childhood Cancer Study Investigators. The United Kingdom childhood cancer study: objectives, materials, methods. British J. Cancer 2000; 82(5), 1073-1102. 3. UK Childhood Cancer Study Investigators (writing committee: Law GR, Smith AG, Roman E) The importance of full participation: lessons from a national case-control study. British J. Cancer 2002; 86(3), 350-355. Competing interests: None declared |
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L. Travis Haws, Dentist Lakewood CO 80228
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Peter Ivanoski states, with concern, and references: >>>"Before 1920, acute leukemia among children was a rare event. A significant peak-age incidence (2-5 years) appeared after 1940. Since then, the incidence rate of childhood leukemia has been more or less remarkably stable. This means that some leukemogenic factor must have been introduced in children's lives some time around 1940. It is a highly striking coincidence that at the same year the introduction of immunization against diphtheria was began on a national scale."<<< I wonder if our friends at the CDC, NIH, WHO etc. have considered adding leukemia in addition to diabetes, Guillian-Barre', Autism, SIDS, Arthritis, Thrombocytopenia, Encephalitis, Death, SBS, Distressed Breathing, Thimerosal Accumulation in Brain (TAB) (1), delayed speech, tics, seizures, hallucinations, diziness, Hemorrhagic Vasculomyelinopathy etc. etc. etc. to "highly coincidental" adverse reactions from the long list of mass immunizations. Do you think parents would be informed during their child's well visit...of any of the above? Well, at least they were "well"...or should have been prior to the inoculation(s). That is unless you follow most vacccinators advice. In particular, MMR advice from WHO is to jab unless the child is in serious risk of dying. And the only reason given not to jab in this instance is that the death may "incorrectly" be attributed to the MMR. (2) And we wonder why most all serious adverse vaccine reactions are attributed to "coincidence". As clearly seen in this WHO advice--take great lengths to disclaim any adverse vaccine reaction. Back to the leukemia aspect. If consently informed, would you opt for the risk of a cough with a grayish film covering the throat and small risk of death or serious chronic illness sequelae (usually cardiac) from diphtheria (mostly for the malnourished, immunocompromised or poorly managed), or the small risk of a "coincidental" vaccine induced leukemia (and all its associated "goodies")? What about the novel, yet to be seen vaccine derived, serious illnesses that seem to keep popping up out of the blue? Do you want to risk those (keeping in mind we're not looking for the vaccine correlation and if we find it, we'll certainly hide it), or risk an illness you are hopefully familiar with? 1) http://ehp.niehs.nih.gov/members/2005/7712/7712.pdf Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal; Thomas M. Burbacher, Danny D. Shen, Noelle Liberato, Kimberly S. Grant, Elsa Cernichiari, and Thomas Clarkson 2) Bulletin of the World Health Organisation, 1997; 75 (4) page 371 Competing interests: None declared |
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Michael D Innis, Director Medisets International Home 4575
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Editor, Responding to the report by Gilham et al; [1] I draw attention to a letter entitled “Immunization and Childhood Leukaemia” [2] in which it was shown that Leukaemia in children in Brisbane Children’s Hospital from 1958 to 1964 showed a significant statistical association with immunization against diphtheria, tetanus and whooping cough. In the letter it was stated, “since antigenic stimulation is known to cause hyperplasia of mammalian lymphoreticular tissue, and since such hyperplasia may in some strains of mice, proceed to malignant neoplasia [3] the possibility that a similar mechanism could operate in children submitted to the repeated antigenic stimulation inherent in immunization, seemed worth investigating.” In view of Dr Ivanovski’s observations that the incidence of childhood leukaemia increased with the introduction of DPT vaccination [4] it is virtually certain that, if Gilham et al; investigated the immunization status of the children in their two groups, they will find the group with Leukaemia also shows a statistically significant increase in immunization with DPT vaccine. This would then call not for rejection, but for a future redefinition of vaccination schedules, as Dr Ivanovski says. Michael Innis References: 1. Gilham, J Peto, J Simpson, E Roman, T O B Eden, M F Greaves, F E Alexander, BMJ, 1:10.1136/bmj.38428.521042.8F (published 22 April 2005) 2. Innis MD Immunization and Childhood Leukaemia Lancet Letter to the Editor March 13th 1965 i 605 3. Metcalfe D. Brit. J. Cancer 1961; 15:769 4. Ivanovski P. Prevention of Childhood Leukaemia: Is it possible BMJ Rapid Response 5th May 2005 Competing interests: As previously declared |
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James E Parker, Retired Paediatrician 289 McCallum Rd Abbotsford BC CANADA V2S 8A1
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With respect I would suggest that Drs Ivanoski (Rapid Response 5 May 2005) and Innis (26 May 2005) miss the point of Gilham et al's article when they invoke infant immunization in the aetiology of leukaemia by the introduction of a 'red herring'. The discovery by Greaves of disease markers on Guthrie cards and cord blood suggests a period of long latency in childhood leukaemia in relation to the 'childhood peak'. These markers were present BEFORE the individual administration of DPT immunization. James E Parker Competing interests: None declared |
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Michael D Innis, Director Medisets International Home 4575
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Editor, Firstly let me apologize for not heeding your advice to read carefully one’s response before clicking the ‘submit’ button. I failed to do so in my last response and hence Leukaemia became Leukarmia. Now to answer Dr James E Parker who can see a “red herring” in my response. I have explained how I arrived at this conclusion[1]. Some of your readers may recognize my explanation as an example of ‘Ampliative Induction’[2]. Having declared my position [3] it is up to Dr C Gilham and co- authors[4] to prove I am wrong. They can do this very easily by showing there is no significant statistical association between Acute Lymphoblastic Leukaemia and DPT vaccine in the children they report. I await their verdict. After 40 years of waiting I can wait a little longer. Michael Innis References: 1.Innis MD. Rapid Response 26th May 2005 2.Kneale W Probability and Induction 2nd Impression 1963 pp 56-60 Oxford University Press Amen House London E C 4 3.Innis MD Immunization and Childhood Leukaemia Lancet Letter to the Editor March 13th 1965 i 605 4.Gilham C, Peto J, Simpson J, Roman E et al; Day care in infancy and risk of childhood acute lymphoblastic leukaemia:findings from UK case- control study. BMJ, Apr 2005; 10.1136/bmj.38428.521042.8F. Competing interests: As previously declared |
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Maureen Asbury, President Trentham Environmrntal Action Group
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Online publication of this paper by Gilman et al on 22nd April was accompanied by extensive press coverage to the effect that the paper also showed that electromagnetic fields, such as from powerlines, background radiation and vitamin K are not causes of childhood leukaemia. We would like to point out that none of these agents are mentioned in the paper by Gilman et al, which is confined to cancer rates in infants attending day care centres. A pooled analysis by Professor Anders Ahlbom et al (British Journal of Cancer September 2000), which included the results of a UKCCS powerlines study, found a doubling of the risk of childhood leukaemia with magnetic field exposure above 0.4 microtesla, well below the levels seen near powerlines. The separate results of the UKCCS study alone were subsequently published in the British Journal of Cancer in November 2000. This study found 40% more cases than controls near powerlines in the UK. We also point out that the Dr Gerald Draper et al have recently published their work (British Medical Journal 3rd June) showing increased incidence of childhood leukaemia up to 600 metres from 400 and 275 kV powerlines in the UK where they also cite the above results of the UKCCS 2000 study. Competing interests: None declared |
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Michael J O'Carroll, Professor Emeritus University of Sunderland (home address) Garden House, Welbury, Northallerton DL6 2SE
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Comment on Gilham et al (UKCCS) BMJ 22 April 2005 [reference BMJ, doi:10.1136/bmj.38428.521042.8F (published 22 April 2005)]. The summary box on what was already known, before this study, starts with "Childhood leukaemia is a biologically diverse disease and is likely to arise by several aetiological pathways". This study adds rather striking statistical results to support the first of the two parts of the infection hypothesis; that is the Greaves hypothesis that infant deficit of exposure to infection (and consequent deficit in immune development) increases the risk of ALL. Implicitly this finding therefore also lends support to the second part: the Kinlen hypothesis that childhood exposure to infection through population mixing increases the risk of ALL. The study reflects the multifactorial nature of the immune system and how it deals with stresses which may lead to leukaemia. It thereby reinforces the opening statement from the summary box, that childhood leukaemia is likely to arise by several aetiological pathways. Among them may be pathways involving infection in combination with non-infection exposures which interfere with the immune system. Thus by strengthening the infection hypothesis, the study adds to the case for involvement of the several non-infection exposures which have some evidence of association, such as aspects of diet or the IARC category 2B electromagnetic fields (EMF) among others. On the other hand, for cases with pre-leukaemic genetic damage, the study has no bearing on the aetiology of the genetic damage in utero. In this respect EMF may be further implicated by the results of Draper et al, BMJ vol. 330, 1290 - 1293, 4 June 2005. Gilham et al do not show that non-infection mechanisms and causal factors are not at work, but rather their study enhances the prospects for them. It is surprising therefore that media responses to this study, including scientific media, with whatever encouragement, have made such statements as "there is no association between exposure to electromagnetic fields and the risk of childhood leukaemia" and generally seemed to champion the infection hypothesis to the exclusion of other factors, which might be all the more relevant in combination with infection. The findings in this paper need to be honed and replicated of course (and how often has that been demanded of EMF findings!), but the statistical results are striking, to use a word implied by the authors. I found the smoothness and consistency of the results slightly surprising given the rough nature of the proxies for social interaction. Could the authors have made an error in respect of the counter- expectation result on groups with and without older siblings? They say "The odds ratio for formal day care was 0.61 (0.42 to 0.87) for ALL in children without older siblings and 0.38 (0.26 to 0.54) for those with older siblings, a non-significant difference in the opposite direction to that anticipated." The overlap of confidence intervals (as in 0.42 < 0.54) does not necessarily mean the difference was non-significant; it only suggests less significant than p = .05 squared (p = .0025). As the odds ratio for each group falls outside the confidence interval for the other (as in .38 < .42), the result appears significant, though this is not material to the main conclusions of the study. M J O’Carroll 19 June 2005 Competing interests: None declared |
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Trevor S Parry, A/Professor School of Paediarics and Child Health,University of Western australai, 6008
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The article by Gilham et al raises the question as to whether the increased incidence of infections in child care and associated acute leukemia was linked with cortisol levels .There is growing evidence that chronic stress is related to cortisol failing to lower in the usual diurnal patterns with adverse outcomes on health, learning and behaviour. An ongoing West Australian study using salivary cortisol levels as a biomaker taken morning and afternoon on three successive days was linked to Australain standards of quality child care (QAIS). In unsatisfactory child care as determined by these standards there was a failure of the usual decline in afternoon cortisol. However even in those child care centres assessed as 'satisfactory' there was a similar failure of the afternoon decline of salivary cortisol levels in some of the quality criteria that condsidered relationship issues.Could it be that rather than infection being a general concern in child care that there is a link with stress in children and an adverse cortisol response when child care is unsatisfactory. Might this have significant preventive implications both for infection and the reported li nk with acute leukemia? Competing interests: None declared |
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