945
OBSERVED TO EXPECTED RATIOS (O/E) OF CHILDHOOD LEUKAEMIA DEATHS BY RATE OF POPULATION CHANGE
negative correlation) between county standardised morbidity ratios for ALL at ages 1-7 and 8-24:
Data from Cartwnght et al,3 as Spearman rank coefficients for county Standardised morbidity ratios for ALL-
ALL in the childhood peak and amongst older people differs in cell type4 and may have a different aetiology.L5 International incidence data6 show no correlation between ALL at ages 0-4 and 5-24. Our results and these of Kinlen at al suggest that there may even be a negative association. Community characteristics are determinants of ALL incidence in young people2,6,7 and the emergence of the childhood peak has been associated with aspects of national development.8 Little attention has been paid to effects of community characteristics on age-specific patterns within developed societies. Earlier studies have, however, demonstrated that the childhood peak is more pronounced for rural communities and those with lower socioeconomic status: Ratio Age 1-00*, 0-4yr; 0-89, 5-9 yr; 0-81 10-14yr (a) Rural:urban, mortality (b) Rural:urban, incidence 1-00*, 0-S yr; 0-45, 6-14 yr (c) Lower:upper socioeconomic 1-00*, 0-4 yr; 0-71, 5-9 yr; 0 39, 10-15yr group incidence ia) USA 1944-48 (Pulb Health Rep 1956; 71: 103) (b) Northumberland and Durham, UK 1951-60 (Br F Prev Soc Med 1965; 18: 14). (C) Buffalo, NY, USA 1943-56 (Cancer 1959; 12: 351). *Reference group ratio, standardised to 1-00.
Similar relationships are now seen for rural new towns (Kinlen et al) and isolated communities.2 Thus the results of Kinlen et al form part of a body of evidence indicating that community lifestyle characteristics show distinct relations to ALL in the childhood peak. Whether the differences between this age group and other young people have a causal explanation or are consequences of differing aetiologies is an open question. Kinlen et al suggest that the deficit at ages 5-24 in the new towns is attributable to an immunising effect of limited exposure to a specific infectious agent or agents and see this as supporting their hypothesis that such an agent can cause leukaemia. Future studies on incidence data should be extended to include lymphoid malignancies. The late host response model for Hodgkin’s disease predicts that incidence is high in young people who are recent migrants and low in those whose early childhood has been spent in a new town. University of Leeds, Department of Pathology, Leeds LS2 9NG, UK
FREDA E. ALEXANDER PATRICIA A. MCKINNEY
Speculations on the cause of childhood acute lymphoblastic leukaemia. Leukaemia 1988; 2: 120-25. 2 Alexander FE, Ricketts TJ, McKinney PA, Cartwnght RA. Community lifestyle characteristics and risk of acute lymphoblastic leukaemia in children. Lancet (in 1 Greaves MF.
unrecognised infection, the transmission of which is facilitated by population mixing. However, new towns have not been the only places to experience rapid growth. Interest in the possible role of population mixing was aroused by the excess of leukaemia recorded near nuclear establishments that had experienced large influxes of population.! We have looked at leukaemia mortality rates in rapidly growing areas, irrespective of whether they are new towns. Data on leukaemia deaths in all 1366 local authority areas in England and Wales are available for the period 1969 to 1973.2 The table shows the ratio of observed to expected numbers of deaths for all types of leukaemia for areas experiencing different rates of population change between 1961 and 1971. The categories of population change were decided on before inspection of the mortality data. The expected numbers of deaths were calculated by applying national rates to the local population at risk as recorded in the 1971 census. In both the 0-4 and the 5-14 age groups and for the 0-14 group as a whole the highest ratio of observed to expected deaths (O/E) was in the areas of greatest population growth. Confidence intervals (CI), based on the Poisson distributionshow that the excess was significant at the 0-05 level for those aged 5-14 (95% CI 1-08-1-91) and for the 0-14 group as a whole (1-10-1 72), but not for the youngest age group (O.86-1.81). There were no significantly high or low O/E ratios in groups of areas of lower population change. We take these results to support the view that some factor associated with rapid population growth is involved in the aetiology of childhood leukaemia. School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ, UK
1. Kinlen L. Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites sites in Britain. Lancet 1988; ii: 1323-27. 2. Office of Population Censuses and Surveys. Area mortality decennial supplement 1969-1973, England and Wales: urban areas, rural areas microfiches. London: HM Stationery Office, 1981. 3. Bailar JC, Ederer F. Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 1964; 20: 639-43.
Toxicity of D-lactate
press). 3
Cartwright RA, Alexander FE, McKinney PA, Ricketts TJ, Hayhoe FGJ, Clayton
DGC. Leukaemia and lymphoma. an atlas of distribution within areas of England and Wales 1984-1988. London Leukaemia Research Fund, 1990. 4 Greaves MF, Pegram S, Chan IC. Collaborative group study of the epidemiology of acute lymphoblastic leukaemia subtypes. background and first report. Leuk Res 1985, 9: 715-33. 5 Neglia JP, Severson RK, Linet MS. Towards a testable aetiology of childhood acute
lymphoblastic leukaemia
Leukaemia 1990, 4: 517-21.
6 Muir CS, Waterhouse J, Mack T, Powell J, Whelan S. Cancer incidence in 5 continents. vol V (IARC Sci Publ no 88) Lyon. International Agency for Research on
Cancer, 1987.
7 Cook-Mozaffari PJ, Darby SC, Doll R, Forman D, Hermon C, Pike MC, Vincent T. Geographical variations in mortality from leukaemia and other cancers in England and Wales in relation to proximity to nuclear installations, 1969-1978. Br J Cancer 1989, 59: 476-85. 8
9
Doll R The epidemiology of childhood leukaemia. J R Stat Soc A 1989; 152: 1-11. Gutensohn N, Cole P. Childhood social environment and Hodgkin’s disease. N Engl J Med 1981; 304: 135-40.
SlR,-Dr Kinlen and colleagues have found an excess of leukaemia deaths for children aged 0-4 years in some British new towns during the period 1946-65. Such areas experienced rapid population growth involving a large influx of people, and Kinlen et al propose that the
excess
of leukaemia may be
a
rare
response to
an
IAN LANGFORD GRAHAM BENTHAM
SIR,-D-lactic acidosis due to abnormal gut flora is a welldocumented late complication of bowel surgery.1 Your Sept 8 editorial (p 599) suggests that the periodic neurological symptoms resembling ethanol intoxication in these patients might be, at least partly, due to the toxic effects of D-lactate. It is interesting to note that in anxiety-prone individuals panic attacks may be provoked by lactate infusions.2 We now propose that abnormal colonisation of the colon, in common with certain dietary habits, might have a pivotal role in the clinical manifestation of panic attacks. Panic attacks in these patients could even be seen as a distinctive psychiatric syndrome of true oroanal origin. Haaga Neurological Rehabilitation Centre, 00321 Helsinki, Finland
E. ELOMAA
Department of Neurology, Hospital, Espoo
K. AHO
Jorvi 1.
2.
Stolberg L, Rolfe R, Gitlin N, et al. D-lactic acidosis due to abnormal gut flora. N Engl J Med 1982; 306: 1344-48 Margraf J, Ehler A, Roth WT Sodium lactate infusions and panic attacks: a review and critique. Psychosom Med 1986; 48: 23-51.
OBSERVED TO EXPECTED RATIOS (O/E) OF CHILDHOOD LEUKAEMIA DEATHS BY RATE OF POPULATION CHANGE
negative correlation) between county standardised morbidity ratios for ALL at ages 1-7 and 8-24:
Data from Cartwnght et al,3 as Spearman rank coefficients for county Standardised morbidity ratios for ALL-
ALL in the childhood peak and amongst older people differs in cell type4 and may have a different aetiology.L5 International incidence data6 show no correlation between ALL at ages 0-4 and 5-24. Our results and these of Kinlen at al suggest that there may even be a negative association. Community characteristics are determinants of ALL incidence in young people2,6,7 and the emergence of the childhood peak has been associated with aspects of national development.8 Little attention has been paid to effects of community characteristics on age-specific patterns within developed societies. Earlier studies have, however, demonstrated that the childhood peak is more pronounced for rural communities and those with lower socioeconomic status: Ratio Age 1-00*, 0-4yr; 0-89, 5-9 yr; 0-81 10-14yr (a) Rural:urban, mortality (b) Rural:urban, incidence 1-00*, 0-S yr; 0-45, 6-14 yr (c) Lower:upper socioeconomic 1-00*, 0-4 yr; 0-71, 5-9 yr; 0 39, 10-15yr group incidence ia) USA 1944-48 (Pulb Health Rep 1956; 71: 103) (b) Northumberland and Durham, UK 1951-60 (Br F Prev Soc Med 1965; 18: 14). (C) Buffalo, NY, USA 1943-56 (Cancer 1959; 12: 351). *Reference group ratio, standardised to 1-00.
Similar relationships are now seen for rural new towns (Kinlen et al) and isolated communities.2 Thus the results of Kinlen et al form part of a body of evidence indicating that community lifestyle characteristics show distinct relations to ALL in the childhood peak. Whether the differences between this age group and other young people have a causal explanation or are consequences of differing aetiologies is an open question. Kinlen et al suggest that the deficit at ages 5-24 in the new towns is attributable to an immunising effect of limited exposure to a specific infectious agent or agents and see this as supporting their hypothesis that such an agent can cause leukaemia. Future studies on incidence data should be extended to include lymphoid malignancies. The late host response model for Hodgkin’s disease predicts that incidence is high in young people who are recent migrants and low in those whose early childhood has been spent in a new town. University of Leeds, Department of Pathology, Leeds LS2 9NG, UK
FREDA E. ALEXANDER PATRICIA A. MCKINNEY
Speculations on the cause of childhood acute lymphoblastic leukaemia. Leukaemia 1988; 2: 120-25. 2 Alexander FE, Ricketts TJ, McKinney PA, Cartwnght RA. Community lifestyle characteristics and risk of acute lymphoblastic leukaemia in children. Lancet (in 1 Greaves MF.
unrecognised infection, the transmission of which is facilitated by population mixing. However, new towns have not been the only places to experience rapid growth. Interest in the possible role of population mixing was aroused by the excess of leukaemia recorded near nuclear establishments that had experienced large influxes of population.! We have looked at leukaemia mortality rates in rapidly growing areas, irrespective of whether they are new towns. Data on leukaemia deaths in all 1366 local authority areas in England and Wales are available for the period 1969 to 1973.2 The table shows the ratio of observed to expected numbers of deaths for all types of leukaemia for areas experiencing different rates of population change between 1961 and 1971. The categories of population change were decided on before inspection of the mortality data. The expected numbers of deaths were calculated by applying national rates to the local population at risk as recorded in the 1971 census. In both the 0-4 and the 5-14 age groups and for the 0-14 group as a whole the highest ratio of observed to expected deaths (O/E) was in the areas of greatest population growth. Confidence intervals (CI), based on the Poisson distributionshow that the excess was significant at the 0-05 level for those aged 5-14 (95% CI 1-08-1-91) and for the 0-14 group as a whole (1-10-1 72), but not for the youngest age group (O.86-1.81). There were no significantly high or low O/E ratios in groups of areas of lower population change. We take these results to support the view that some factor associated with rapid population growth is involved in the aetiology of childhood leukaemia. School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ, UK
1. Kinlen L. Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites sites in Britain. Lancet 1988; ii: 1323-27. 2. Office of Population Censuses and Surveys. Area mortality decennial supplement 1969-1973, England and Wales: urban areas, rural areas microfiches. London: HM Stationery Office, 1981. 3. Bailar JC, Ederer F. Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 1964; 20: 639-43.
Toxicity of D-lactate
press). 3
Cartwright RA, Alexander FE, McKinney PA, Ricketts TJ, Hayhoe FGJ, Clayton
DGC. Leukaemia and lymphoma. an atlas of distribution within areas of England and Wales 1984-1988. London Leukaemia Research Fund, 1990. 4 Greaves MF, Pegram S, Chan IC. Collaborative group study of the epidemiology of acute lymphoblastic leukaemia subtypes. background and first report. Leuk Res 1985, 9: 715-33. 5 Neglia JP, Severson RK, Linet MS. Towards a testable aetiology of childhood acute
lymphoblastic leukaemia
Leukaemia 1990, 4: 517-21.
6 Muir CS, Waterhouse J, Mack T, Powell J, Whelan S. Cancer incidence in 5 continents. vol V (IARC Sci Publ no 88) Lyon. International Agency for Research on
Cancer, 1987.
7 Cook-Mozaffari PJ, Darby SC, Doll R, Forman D, Hermon C, Pike MC, Vincent T. Geographical variations in mortality from leukaemia and other cancers in England and Wales in relation to proximity to nuclear installations, 1969-1978. Br J Cancer 1989, 59: 476-85. 8
9
Doll R The epidemiology of childhood leukaemia. J R Stat Soc A 1989; 152: 1-11. Gutensohn N, Cole P. Childhood social environment and Hodgkin’s disease. N Engl J Med 1981; 304: 135-40.
SlR,-Dr Kinlen and colleagues have found an excess of leukaemia deaths for children aged 0-4 years in some British new towns during the period 1946-65. Such areas experienced rapid population growth involving a large influx of people, and Kinlen et al propose that the
excess
of leukaemia may be
a
rare
response to
an
IAN LANGFORD GRAHAM BENTHAM
SIR,-D-lactic acidosis due to abnormal gut flora is a welldocumented late complication of bowel surgery.1 Your Sept 8 editorial (p 599) suggests that the periodic neurological symptoms resembling ethanol intoxication in these patients might be, at least partly, due to the toxic effects of D-lactate. It is interesting to note that in anxiety-prone individuals panic attacks may be provoked by lactate infusions.2 We now propose that abnormal colonisation of the colon, in common with certain dietary habits, might have a pivotal role in the clinical manifestation of panic attacks. Panic attacks in these patients could even be seen as a distinctive psychiatric syndrome of true oroanal origin. Haaga Neurological Rehabilitation Centre, 00321 Helsinki, Finland
E. ELOMAA
Department of Neurology, Hospital, Espoo
K. AHO
Jorvi 1.
2.
Stolberg L, Rolfe R, Gitlin N, et al. D-lactic acidosis due to abnormal gut flora. N Engl J Med 1982; 306: 1344-48 Margraf J, Ehler A, Roth WT Sodium lactate infusions and panic attacks: a review and critique. Psychosom Med 1986; 48: 23-51.
