BMJ No 7093 Volume 314
Letters Saturday 24 May 1997
Leukaemia near La Hague nuclear plant
Bias could have been introduced into study
Editor,Dominique Pobel and Jean-François Viel found an association between going to the beach more than once a month and leukaemia risk, with an odds ratio of 2.87.(1) Eighty two out of 192 controls were engaged in this activity. If this association were causal, we could expect, roughly, a twofold increase in the incidence of childhood leukaemia in the Nord-Cotentin. Previously, however, the authors had observed an incidence similar to the expected figures (standardised incidence ratio of 1.1),(2) which suggests that a bias could have been introduced in the study design. This issue should be systematically and carefully investigated.
A recall bias could not be ruled out. A selection bias
may easily occur since the source population used for identifying
c Although the differences are not statistically significant, fathers of
cases were ranked in higher social categories than fathers of controls.
Some additional criteria would also be useful for comparing cases and
controls. For instance, did the controls live farther from the beaches
than cases, conditionally on matching? Did they live in similarly sized
communities?
To what extent are the variables of interest correlated-mothers'
seaside activity during pregnancy, children's seaside activity,
consumption of local shellfish, living in a granite house? To what
extent are these variables correlated with the distance between the
subjects' homes and the beach or with social category or any other
characteristic? Numbers allow adjustments, at least when dichotomous
variables are used; could the authors show such multivariate analysis?
The authors say they found an excess of childhood leukaemia in the
electoral ward containing the reprocessing plant; in a previous
paper(2) they reported four cases in this ward from 1978 to
1992 versus 1.4 expected. The four case children played on the beach at
least once a month; what about the controls in this ward?
Jacqueline Clavel
Department of Epidemiological and Statistical Research on
Environment and Health, References
1 Pobel D, Viel J-F. Case-control study of leukaemia among
young people near La Hague nuclear reprocessing plant: the
environmental hypothesis revisited. BMJ
1996;314:101-6. (11 January.)
2 Viel J-F, Pobel D, Carré A. Incidence of leukaemia around La
Hague nuclear waste reprocessing plant: a sensitivity analysis.
Stat Med 1995;14:2459-72.
The study region was restricted to a circle (diameter 35 km)
around the La Hague reprocessing plant. Since their original aim was to
investigate the apparent increase in incidence of leukaemia in the
vicinity of the plant,(2) the design of the study was not
ideal for examining recreational activities and food consumption. Cases
and controls were tightly matched on geographical region at diagnosis
and loosely matched for age. The exposure of interest, parents' recall
of their own and their children's dietary and recreational behaviour,
may have occurred 30 years or more in the past. Further, there was
little information about the control families who refused to
participate.
Of the 27 patients ascertained during the 16 year study period, six
were young adults (not children) and two had chronic myeloid leukaemia.
Given the wide age range, the different diagnostic groups, the small
size of the sample, and the multiple tests performed (173 exposure
items with one or more methods of testing), we believe that these
findings warrant a far more cautious interpretation. Further, the
findings rely heavily on tests for trend, which seem predominantly to
have been applied even when associations were not statistically
significant. The trend statistic is not a traditional epidemiological
tool and requires justification under these circumstances. As an
example, the figure gives 95% confidence intervals of the relative
risk estimates for offspring's recreational activity on local beaches
(from Pobel and Viel's table 4). The lower limits are all below
1, and other dose-response relations, other than a positive linear
trend, could fit within the range of each
estimate.
Although the possibility that novel pathways of the type proposed
should not be discounted,(3) we are not persuaded that Pobel
and Viel's study provides convincing evidence one way or the
other.
Graham Law
Eve Roman
Leukaemia Research Fund Centre for Clinical Epidemiology,
References
1 Pobel D, Viel J-F. Case-control study of leukaemia among
young people near La Hague nuclear reprocessing plant: the
environmental hypothesis revisited. BMJ
1997;314:101-6. (11 January.)
2 Viel J-F, Pobel D. Incidence of leukaemia in young people around
the La Hague nuclear waste reprocessing plant: a sensitivity analysis.
Stat Med 1995:14:2459-72.
3 Urquhart J D, Black R J, Muirhead M J, Sharp L, Maxwell M, Eden O B,
et al. Case-control study of leukaemia and
non-Hodgkin's lymphoma in children in Caithness near the Dounreay
nuclear installation. BMJ 1991:302:687-92.
In an equivalent case-control study conducted around Sellafield,
west Cumbria, Gardner et al found no associations
between childhood leukaemia and these lifestyle factors when using the
appropriate 'local' control group, and they drew attention to the
'low quality' of data based entirely on questionnaires because of
the real (and unquantifiable) possibility of recall bias.(2)
This must be particularly so for births over a period of almost 40
years, as in the La Hague study.
Further, Pobel and Viel do not refer to the vast amount of relevant
research carried out on environmental radioactivity over the past
decade, which has been summarised recently by reports from the National
Radiological Protection Board and the Committee on Medical Aspects of
Radiation in the Environment (COMARE).(3) COMARE concluded
that radiation doses due to discharges are 'far too small' to
account for the excess of childhood leukaemia near Sellafield. Although
Pobel and Viel note the results of the case-control study conducted
around Dounreay in Caithness, in which an association between leukaemia
and the use of local beaches by children (again based solely on
questionnaire data) was also found, they do not refer to the subsequent
detailed investigation in the Dounreay area by Watson and Sumner, who
carried out a sophisticated programme of measurements of radioactivity
in children who had been diagnosed with leukaemia and in unaffected
children.(4) They found no indication of unusual levels
of radioactivity.
Set against the weak and inconsistent epidemiological evidence for an
effect of environmental radioactivity on childhood leukaemia in the
vicinity of reprocessing plants is the evidence for the influence of
unusual population mixing in these areas, of which Pobel and Viel make
no mention. Kinlen has produced compelling evidence from a series of
studies for the impact on childhood leukaemia of the mixing of urban
and rural populations.(5) Indeed, given this evidence, it
would be surprising if the large construction projects at La Hague and
at nearby sites had not raised the risk of childhood leukaemia in this
area. The potentially important effect of population mixing on the
communities surrounding La Hague should at least have been
noted.
Richard Wakeford
British Nuclear Fuels, References
1 Pobel D, Viel J-F. Case-control study of leukaemia among
young people near La Hague nuclear reprocessing plant: the
environmental hypothesis revisited. BMJ
1997;314:101-6. (11 January.)
2 Gardner M J, Snee M P, Hall A J, Powell C A, Downes S, Te
3 Committee on Medical Aspects of Radiation in the Environment
(COMARE). Fourth report. The incidence of cancer and leukaemia
in young people in the vicinity of the Sellafield site, west Cumbria:
further studies and an update of the situation since the publication of
the report of the Black Advisory Group in 1984. Wetherby:
Department of Health, 1996.
4 Watson W S, Sumner D J. The measurement of radioactivity in people
living near the Dounreay nuclear establishment, Caithness,
Scotland. Int J Radiat Biol 1996;70:117-30.
5 Kinlen L J. Epidemiological evidence for an infective basis in
childhood leukaemia. Br J Cancer 1995;71:1-5.
To view table click here.
Anxieties have been raised again in the local community by media
reports of uranium contamination at the former Greenham Common airbase
and a newspaper report of increased mortality from childhood leukaemia
at Newbury. In view of this we have collated our clinic figures for a
further 11 years, giving data for the whole of west Berkshire for 25
years (table 1). The findings for the two periods are similar, although
data for 1986-96 may be incomplete since some children resident in the
study area may not have been treated at our clinic. There was no
increase in the relapse rate or death rate in those with acute
lymphoblastic leukaemia, who have been entered into Medical Research
Council trials since 1972 (S Richards, personal
communication).
Further studies are planned with the Childhood Cancer Research Group,
the Oxford Cancer Intelligence Unit, the Newbury Leukaemia Study Group,
and the Berkshire Health Authority. We will assess whether the
additional and original cases are geographically related to Greenham or
the Atomic Weapons Establishments plants and extend the age range
studied to 25. It would be interesting to re-examine the incidence of
childhood cancer in the same areas of west Berkshire, as a previous
report suggests that the incidence of solid tumours is also
raised.(4) We hope that some reason or environmental cause
can then be postulated.
Carol Barton
Royal Berkshire Hospital,
References
1 Pobel D, Viel J-F. Case-control study of leukaemia among
young people near the La Hague nuclear reprocessing plant: the
environmental hypothesis revisited. BMJ
1997;314:101-106. (11 January.)
2 Roman E, Watson A, Beral V, Buckle S, Bull D, Bauer K, et
al. Case control study of leukaemia and non-Hodgkins lymphoma
among children age 0-4 living in W. Berks. and N. Hants. Health
Districts. BMJ 1993;306:615-621.
3 Roman E, Beral V, Carpenter L, Watson A, Barton C, Ryder H,
et al. Childhood leukaemia in the West Berkshire and
Basingstoke and North Hampshire District Health Authorities in relation
to nuclear establishments in the vicinity. BMJ
1987;274:597-602.
4 Committee on Medical Aspects of Radiation in the Environment.
Third report. Report on the incidence of childhood cancer in the
West Berkshire and North Hampshire area, in which are situated the
Atomic Weapons Research E
After Chernobyl, I went to contaminated places in Sweden and the
Ticino area of Switzerland to look at leafbugs. In summer 1987 I
started to collect leafbugs in the areas of Osterfarnebo and Gavle in
Sweden and Mendrisiotto in Switzerland, and brought back two pairs of
Drosophila melanogaster, which I bred in my kitchen as
was done in the laboratory. From the first generation I found many
deformations of the eyes, antennae, vibrissae, bristles, segments of
the abdomen, and wings. The leafbugs were mostly deformed on their
antennae, wings, and legs. In Sweden I also found plants with leaf
colour changed from green to dark red or changed colour of flowers; I
found heavily deformed leaves in Sweden and in the Ticino.
Since 1993 I have been studying leafbugs in the canton of Aargau,
Switzerland, which contains four nuclear power plants and one research
plant. I collect 65 leafbugs at each of 40 points. The insects with the
greatest deformities are found close (5-10 km) to the plants, to the
east, southeast, and south; less severe, but frequent, deformations are
found southwest of the plants.
In my work, I document not just the quantity but also, by painting the
deformed leafbugs, the quality of the deformations. When I have
published my work in Switzerland, suggesting that there is a connection
between low level radiation from the nuclear plants and the
malformations, I have been heavily attacked by scientists. Cornelia Hesse-Honegger
Feldeggstrasse 21,
1 Pobel D, Viel J-F. Case-control study of leukaemia among
young people near La Hague nuclear reprocessing plant: the
environmental hypothesis revisited. BMJ
1997;314:101-6. (11 January.)
Although I have already addressed this issue,(1) they
still want to know if the controls live farther from the beaches than
cases, but this time conditionally on matching. The results remain
non-significant for the closest coast, Vauville beach, and
Urville-Nacqueville beach (P=0.43, 0.18, and 0.76, respectively).
Among the four significant exposures (use of local beaches by mothers,
use of beaches by children, consumption of local fish by children, and
children living in a granitic area), only the first two were
significantly correlated (P0.0001); no other pairwise test yielded
significant results among controls (0.65gPg0.24). In the electoral
ward containing the reprocessing plant, all of the four case children
played on the beach at least once a month, whereas only 14 of the 33
controls did so (P=0.05). The independent role played by each of the
three children's factors is confirmed by a multivariate analysis
despite a lack of statistical power on this small dataset (odds ratios:
fish consumption=7.01, P=0.05; beach activity=2.56, P=0.09; granitic
area=4.15, P=0.05).
Graham Law and Eve Roman have commented on the parents' recall.
Exposures may have occurred far in the past and, as in almost every
study, some degree of misclassification is inevitable. But the
reliability of maternally reported information, in a similar context,
has recently been shown to be affected little by time from birth or
determination of case-control status.(2) Moreover, media
coverage on leukaemia clusters around nuclear facilities had never
occurred in France before, nor had a possibility of marine
contamination been put forward. Hence, misclassification would be
random with regard to case status and should tend to obscure rather
than create associations.
Richard Wakeford sets his hopes on the viral hypothesis. Even if a
candidate virus is still to be found, and if the British evidence is
not so compelling, this is at variance with some French
findings.(3)
I hope this additional information will convince the authors that
selection or recall biases are unlikely, and that new methods for
identifying the environmental pathways are warranted.
Jean-François Viel
Department of Public Health, Faculty of Medicine,
References
1 Viel J-F. Criticism of study of childhood leukaemia near
French nuclear reprocessing plant is unfounded. BMJ
1997;314:301.
2 Olson J E, Shu X O, Ross J A, Pendergrass T, Robison L L. Medical
record validation of maternally reported birth characteristics and
pregnancy related events: a report from the Children's Cancer Group.
Am J Epidemiol 1997;145:58-67.
3 Laplanche A, de Vathaire F. Leukaemia mortality in French
communes (administrative units) with a large and rapid population
increase. Br J Cancer 1994;69:110-3.
Researcher
Denis Hémon
Head
INSERM,
Unit 170,
16 Avenue Paul
Vaillant-Couturier,
94807 Villejuif Cedex,
France
Study design is questionable
Editor,
We were surprised by the strength of Dominique Pobel and
Jean-François Viel's conclusion that 'there is some convincing
evidence in childhood leukaemia of a causal role for environmental
radiation exposure from recreational activities on
beaches.'(1)
Research fellow
Senior lecturer
University of Leeds,
Leeds LS2 9GG
Scientific context is needed
Editor,
Dominique Pobel and Jean-François Viel found associations
between childhood leukaemia and the use of beaches around the La Hague
nuclear fuel reprocessing plant in Normandy by pregnant women and
children and the consumption of local seafood by children, which they
relate to possible exposure to environmental
radioactivity.(1) They do not, however, pay sufficient
attention to the scientific context of their results.
Principal research
scientist
Risley,
Warrington,
Cheshire WA3 6AS
Case-control studies have been done in Britain
Editor,
As authors of a case-control study of leukaemia in children
living near nuclear establishments in southern England, we are
interested in the case-control study of leukaemia in young people near
the La Hague nuclear reprocessing plant.(1) Our study found
no links with environmental factors, despite larger numbers and a
comprehensive structured questionnaire.(2) In our original
report of leukaemia in children age 0-14 years diagnosed between
1972-1985, the excess was most marked in children aged 0-4 years living
within 10 km of the nuclear establishments at Aldermaston and
Burghfield,(3) where a doubling in risk was
found.
Consultant haematologist
Hilary Ryder
Malcolm Sargent
social
worker
Reading,
Berkshire,
RG1 5AN
Deformed insects have been found near nuclear plants
Editor,
Dominique Pobel and Jean-François Viel's article touches on
people's worries about radiation.(1) Before starting to
study deformations induced by radiation I worked as a scientific
illustrator for the University of Zurich for 25 years, mainly for
geneticists and taxonomists, and I had painted leafbugs (Heteroptera)
for 15 years in my spare time. Painting mutant fruitflies
(Drosophilidae) and normal fruitflies of different families was my main
task at the institute and gave me an idea of how nature could look if
we go on polluting our environment as we do.
In 1988 I started to collect leafbugs in the main wind directions of
the nuclear power plants Gosgen and Leibstadt in Switzerland, where I
found the most worrying changes (fig 1). I continued these studies in
Sellafield in 1989, Chernobyl in 1990, Three Mile Island in 1992, and
Krummel in 1995.
Fig 1 - Leafbugs found in the grounds of the Paul Scherrer Institute, Villigen, Switzerland, an institute for nuclear research; painted in 1990-1
Scientific
illustrator
CH-8008 Zurich,
Switzerland
Author's reply
Editor,
Jacqueline Clavel and Denis Hémon seem concerned that, as the
control selection process relied on general practitioners, there may
have been a selection bias. However, the control children were not ill
defined, since any parents of a child fulfilling the matching criteria,
and not children consulting general practitioners, were asked to join
the study. The assumptions about general practitioners' practices are
broadly true in this rural area, but I recognise that the stability of
catchment areas across time cannot be checked.
Professor of
biostatistics and epidemiology
25030
Besançon,
France
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