The incidence of childhood leukaemia around the
 La Hague nuclear waste reprocessing plant
 (France): a survey for the years 1978?1998
 A-V Guizard, O Boutou, D Pottier, X Troussard, D Pheby, G Launoy, R Slama, A Spira,
 and ARKM
 Abstract
 Background?A previous study has sug-
 gested an increased incidence rate of
 leukaemia from 1978 to 1992 in people
 aged 0 to 24 years and living in the vicinity
 of the La Hague nuclear waste reprocess-
 ing plant without considering age and
 cytological type.
 Setting?The Nord Cotentin region
 (France) and the island of Alderney
 (United Kingdom).
 Study objective?To describe the occur-
 rence of leukaemia for each age group and
 cytological type from 1978 to 1998 in the
 same area, using accurate reference inci-
 dence rates and adequate estimation of
 the at risk population.
 Design?A geographical study of inci-
 dence using three zones defined according
 to their distance from the site (0 to 10 km:
 Beaumont-Hague electoral ward, 10 to 20
 km and 20 to 35 km) has been conducted.
 The risk of leukaemia was estimated from
 the standardised incidence ratio (SIR) of
 the number of cases observed to the
 number expected. Exact 95% confidence
 intervals (CI) have been computed.
 Participants?All people under the age of
 25 years living in the study region between
 1978 and 1998.
 Main results?The observed number of
 cases of leukaemia in the study region as a
 whole was consistent with the expected
 value (SIR=1.03; 95%CI: 0.73, 1.41). No
 cases were observed on Alderney. The SIR
 in the Beaumont-Hague electoral ward
 was 2.17 (95%CI: 0.71, 5.07). The highest
 SIR was observed in the 5 to 9 years age
 group (SIR=6.38; 95%CI: 1.32, 18.65). This
 consists in acute lymphoblastic leukaemia
 cases.
 Conclusion?This study indicates an in-
 creased incidence of leukaemia in the area
 situated at less than 10 km from the plant.
 Monitoring and further investigations
 should be targeted at acute lymphoblastic
 leukaemia occurring during the childhood
 incidence peak (before 10 years) in chil-
 dren living near the La Hague site and
 may be other nuclear reprocessing plants.
 (J Epidemiol Community Health 2001;55:469?474)
 The Nord Cotentin region of France has a par-
 ticularly high density of nuclear installations.
 The La Hague nuclear waste reprocessing
 plant, a surface storage facility for nuclear
 waste, the Flamanville nuclear power station
 and the Cherbourg military arsenal are all
 within 20 km of each other.
 The clusters of leukaemia in children and
 young adults discovered near the nuclear
 reprocessing plants of Sellafield (England)1 and
 Dounreay (Scotland)2 have been largely inves-
 tigated. Complete overviews, emphasing the
 crucial role of population movements, have
 been recently published.3 4 In France, several
 epidemiological studies were conducted to
 analyse the mortality rate attributable to
 leukaemia or the leukaemia incidence among
 children and young adults living in the vicinity
 of the La Hague reprocessing plant.5?7 The
 incidence of leukaemia between 1978 and
 1992 in the Beaumont-Hague electoral ward
 (10 709 inhabitants in 1990), in which the
 plant is situated was found to be higher than
 expected (4 cases observed versus 1.4 ex-
 pected; standardised incidence ratio (SIR)
 =2.8; 95% confidence intervals (95%CI): 0.8,
 7.2).7 In this paper, the expected numbers of
 cases were calculated with reference rates
 based on small population size and short
 period (1978?1982) and person years were
 estimated by linear interpolation and extrapo-
 lation methods. This observation led to a case-
 control study that showed that the occurrence
 of leukaemia was associated with the mother,
 while pregnant, or the children themselves,
 going to the beach, and the children eating
 locally caught fish and shellfish.8 These find-
 ings have been much debated especially
 concerning choice of the controls, possible
 recall bias, number of associations tested and
 interpretation of the results.9?13 They reinforced
 the misgivings of the local population.
 The La Manche cancer register (ARKM)
 has been collecting extensive data on sex, age,
 cytological type and case history in the ?d?par-
 tement? (county) since 1994. It has also access
 to a professional relations network allowing the
 incidence of child and young adult leukaemia
 in Nord Cotentin to be determined retrospec-
 tively. In the context of an increased childhood
 and young adulthood leukaemia incidence rate
 in the small Beaumont-Hague electoral ward,
 the aim of this study was first to extend the
 surveillance time period by 40% and to
 describe the incidence of leukaemia in the
 Nord Cotentin region between 1978 and 1998,
 with more accurate estimation of the expected
 number. Secondly, the extension of the study
 period permitted the data to be analysed by age
 and cytological type, which provides guidance
 for further aetiological investigations.
 J Epidemiol Community Health 2001;55:469?474 469
 Registre des cancers
 de La Manche
 (ARKM), h?pital Louis
 Pasteur, Cherbourg,
 France
 A-V Guizard
 INSERM Research
 Unit 292, Facult? de
 M?decine Paris-Sud,
 82, rue du G?n?ral
 Leclerc, 94276 Le
 Kremlin Bic?tre
 Cedex, France
 O Boutou
 R Slama
 A Spira
 GRECAN, UPRES EA
 1772, Universit? de
 Caen, Caen, France
 D Pottier
 INSERM CJF 9603,
 Centre
 Hospitalo-Universitaire
 C?te de Nacre, Caen,
 France
 G Launoy
 Laboratoire
 d?h?matologie, Centre
 Hospitalo-Universitaire
 C?te de Nacre
 X Troussard
 Unit of Applied
 Epidemiology,
 University of the West
 of England, Bristol,
 UK
 D Pheby
 Correspondence to:
 Dr Spira
 (spira@vjf.inserm.fr)
 Accepted for publication
 4 March 2001
 www.jech.com
Methods
 The studied region lies within 35 km of the La
 Hague nuclear reprocessing plant. It was
 divided into three zones according to the
 distance from the plant: 0 to 10 km
 (Beaumont-Hague electoral ward), 10 to 20
 km and 20 to 35 km.7 The incidence of leukae-
 mia in the 0 to 24 year old age group living on
 one of the Channel Islands, Alderney (UK),
 situated at 15 km from the site was also inves-
 tigated. The study period covered the years
 1978 to 1998. Before 1978, patient files were
 impossible to trace retrospectively.
 COLLECTION AND VALIDATION OF CASES
 Cases were all individuals aged between 0 and
 24 years old diagnosed with leukaemia between
 the 1 January 1978 and the 31 December
 1998, and living in the study area when
 diagnosed. Cases during the years 1978 to
 1993 were identified by a retrospective survey
 of the 194 doctors who had practised in the
 study area at some time during the period.
 Firstly, the 168 physicians (general practition-
 ers and paediatricians) currently practising in
 the area under study and in the five surround-
 ing electoral wards were asked about cases of
 leukaemia among their patients, the year when
 they started to practise and the name of their
 predecessor. A total of 167 replies were
 obtained: 35 had been practising since before
 1978; 103 between 1978 and 1993 and 19
 since 1993. The replies also named 56
 physicians practising in the area between 1978
 and 1993 and who had subsequently retired or
 moved. These doctors were also contacted.
 The files of hospitals routinely providing
 healthcare for the inhabitants of Nord Cotentin
 were used, as were death certificate data. Cases
 for the period from 1994 onwards were identi-
 fied from the data of the La Manche cancer
 register. Data for Alderney were collected from
 the two general practitioners on the island.
 The cytology of all available blood and/or
 bone marrow samples was examined by one of
 us (XT) to confirm diagnosis. Cases were
 scored as acute lymphoblastic leukaemia, acute
 myeloblastic leukaemia, chronic myeloid leu-
 kaemia or unclassified acute leukaemia accord-
 ing to the French-American-British classifi-
 cation (FAB classification).14
 POPULATION DATA
 The following demographic data were supplied
 by the ?Institut National de la Statistique et des
 Etudes Economiques? (INSEE) for each
 French electoral ward: population by age and
 sex for the years 1975, 1982, and 1990, the
 total population in 1999, and numbers of
 births and deaths by age and sex from 1975 to
 1997. The population for each age, sex and
 electoral ward was estimated for each year by
 aging the population.15 Each of the age cohorts
 was followed up from a census or from birth by
 aging one year at a time, and subtracting the
 number of deaths recorded. The result was
 then corrected by applying the migratory flux
 evenly over the period between censuses and
 for each cohort.
 The total population at risk in the 10
 electoral wards and for the period studied was
 1 287 566 person years (table 1).
 For the island of Alderney, census data for
 age and sex were obtained from the Economics
 and Statistics Unit, Government of Guernsey,
 for the years 1981, 1986, 1991 and 1996. In the
 absence of more detailed data, linear interpola-
 tions and extrapolations were used to estimate
 the size of the inter-census populations (11 300
 person years).
 REFERENCE INCIDENCE RATES
 Reference incidence rates for leukaemia were
 calculated from published general population
 French cancer registers (Bas-Rhin, Doubs and
 Is?re 1978?1992, Calvados 1978?1987, Haut-
 Rhin 1988?1992).16?18 A single reference value
 was calculated for each sex and five year age
 group from the sums of cases and person years
 of all the reference registers (table 2): for the 0
 to 24 year old age group the world standardised
 incidence was 3.42 per 100 000 person years
 for boys and 2.59 per 100 000 person years for
 girls.
 The paediatric registers of Lorraine and of
 the Provence-Alpes-C?te-d?Azur and Corsica
 regions were also used as references for
 children under 15 years old and for the analy-
 sis according to type of leukaemia.19?21
 STATISTICAL METHODS
 It was decided a priori to analyse the data by
 the following age bands: 0 to 4; 5 to 9; 10 to 14;
 15 to 24. Acute lymphoblastic leukaemia cases
 were separately considered for the 1 to 6 year
 old age group, as this age group includes the
 peak incidence reported for this condition.22 23
 Table 1 Population at risk (person years), estimated by the diagonal method for the period
 1978?1998, by age group, sex and zone in Nord Cotentin
 Age (y) Sex
 Distance from the plant
 0 to 10 km 10 to 20 km 20 to 35 km Total (0 to 35 km)
 0 to 4 Male 8 333 76 883 47 206 132 422
 Female 7 926 73 854 45 451 127 231
 Total 16 259 150 737 92 657 259 653
 5 to 9 Male 8 899 73 016 51 303 133 218
 Female 8 618 70 600 49 550 128 768
 Total 17 517 143 616 100 853 261 986
 10 to 14 Male 8 654 69 513 53 936 132 103
 Female 8 312 67 407 52 317 128 036
 Total 16 966 136 920 106 253 260 139
 15 to 19 Male 7 833 68 230 53 367 129 430
 Female 7 186 66 927 50 374 124 487
 Total 15 019 135 157 103 741 253 917
 20 to 24 Male 7 143 72 205 49 533 128 881
 Female 6 521 70 247 46 222 122 990
 Total 13 664 142 452 95 755 251 871
 Total 0 to 24 Male 40 862 359 847 255 345 656 054
 Female 38 563 349 035 243 914 631 512
 Total 79 425 708 882 499 259 1 287 566
 Table 2 Incidence of leukaemia (per 100 000 person years)
 by sex and age group, calculated from 5 French registers
 (Bas-Rhin, 1978?1992; Doubs, 1978?1992; Calvados,
 1978?1987; Haut-Rhin, 1988?1992; Is?re, 1978?1992)
 Sex
 Age (y)
 0 to 4 5 to 9 10 to 14 15 to 19 20 to 24
 Male 5.51 3.23 2.29 2.63 2.65
 Female 4.65 2.11 2.22 1.68 1.55
 Total 5.09 2.68 2.26 2.16 2.11
 470 Guizard, Boutou, Pottier, et al
 www.jech.com
The number of cases expected was calcu-
 lated in the population in each zone studied by
 applying the reference incidence for age and
 sex. The risk of leukaemia in Nord Cotentin
 was estimated from the ratio of the number of
 cases observed to the number expected as a
 SIR. The 95%CI for the SIR were calculated
 assuming that the number of observed cases
 followed a Poisson distribution (Stata 6.0
 software, College Station, Texas). Confidence
 intervals should not be considered as a test of
 statistical significance but as numerical indices
 providing guidance to the selection of impor-
 tant patterns.24
 Results
 There were 38 cases (22 boys and 16 girls) of
 leukaemia recorded between 1978 and 1998 in
 the population of 0 to 24 year olds in the study
 region (see table 3 for details). The first case
 was diagnosed in 1979 and the last in 1998.
 There were 23 cases of acute lymphoblastic
 leukaemia (60.5%), eight of acute myeloblastic
 leukaemia (21.1%), six of chronic myeloid leu-
 kaemia (15.8%) and one of unclassified acute
 leukaemia (2.6%). Five of the cases lived in the
 Beaumont-Hague electoral ward, 16 in the 10
 to 20 km zone and 13 in the 20 to 35 km zone.
 Three of the cases were Down?s syndrome
 patients, none of whom lived in the Beaumont-
 Hague electoral ward. None of the 38 cases had
 a known history of cancer, trisomy 8 syndrome,
 Table 3 Description of leukaemia cases in people under 25 years between 1978 and 1998
 in the study zone
 Case
 number Zone 1* Zone 2* Zone 3*
 Year of
 diagnosis
 Age at
 diagnosis (y) Sex
 Cytological
 type?
 1 ? 79 1 M AML
 2 ? 79 5 M AML
 3 ? 79 19 F CML
 4 ? 80 14 M ALL
 5 ? 80 24 M CML
 6 ? 81 6 M ALL
 7 ? 81 15 F CML
 8 ? 82 3 F ALL
 9 ? 83 6 F ALL
 10 ? 83 22 F AML
 11 ? 84 6 F ALL
 12 ? 84 14 F ALL
 13 ? 85 1 F AL
 14 ? 85 4 M ALL
 15 ? 85 8 F ALL
 16 ? 87 16 F ALL
 17 ? 87 3 M ALL
 18 ? 87 4 M ALL
 19 ? 87 5 F ALL
 20 ? 88 1 M ALL
 21 ? 88 23 M AML
 22 ? 89 5 M ALL
 23 ? 89 1 F ALL
 24 ? 90 12 M ALL
 25 ? 92 1 M ALL
 26 ? 93 2 M ALL
 27 ? 93 18 M CML
 28 ? 93 23 F CML
 29 ? 94 15 F CML
 30 ? 94 6 F ALL
 31 ? 95 12 F ALL
 32 ? 95 12 M AML
 33 ? 95 12 M ALL
 34 ? 97 14 M AML
 35 ? 97 0 M AML
 36 ? 97 20 M ALL
 37 ? 98 5 M ALL
 38 ? 98 15 M AML
 *Zone : 1 : <10 km from the reprocessing plant; 2 : 10 to 20 km from the plant; 3 : 20 to 35 km
 from the plant. ?Type of leukaemia : ALL : acute lymphoblastic leukaemia; AML : acute myelob-
 lastic leukaemia; CML : chronic myeloid leukaemia; AL : unclassified acute leukaemia.
 Tabl
 e
 4
 Numbe
 r
 of
 expecte
 d
 (E
 )
 an
 d
 obse
 rv
 ed
 (O
 )
 case
 s
 of
 leukaemi
 a
 (0
 to
 24
 yea
 r
 olds
 )
 an
 d
 ge
 og
 raphica
 lloc
 atio
 n
 in
 th
 e
 Nor
 d
 Cotenti
 n
 re
 gio
 n
 bet
 w
 ee
 n
 197
 8
 an
 d
 199
 8
 (re
 ferenc
 e
 incidenc
 e
 ra
 te
 s
 fro
 m
 fi
 ve
 gene
 ra
 lcance
 r
 re
 gister
 s,
 se
 e
 tabl
 e
 2)
 Z
 on
 es
 A
 ge
 (y
 )
 0
 to
 4
 5
 to
 9
 10
 to
 14
 15
 to
 24
 Tota
 l0
 to
 24
 O
 E
 S
 IR
 95
 %
 C
 I
 O
 E
 S
 IR
 95
 %
 C
 I
 O
 E
 S
 IR
 95
 %
 C
 I
 O
 E
 S
 IR
 95
 %
 C
 I
 O
 E
 S
 IR
 95
 %
 C
 I
 0
 to
 10
 km
 1
 0.
 83
 1.
 20
 0.
 03
 ,6
 .7
 1
 3
 0.
 47
 6.
 38
 1.
 32
 ,1
 8.
 65
 0
 0.
 38
 0.
 00
 0.
 00
 ,9
 .7
 0*
 1
 0.
 62
 1.
 61
 0.
 04
 ,8
 .9
 9
 5
 2.
 30
 2.
 17
 0.
 71
 ,5
 .0
 7
 10
 to
 20
 km
 4
 7.
 67
 0.
 52
 0.
 14
 ,1
 .3
 4
 3
 3.
 85
 0.
 78
 0.
 16
 ,2
 .2
 8
 5
 3.
 09
 1.
 62
 0.
 53
 ,3
 .7
 8
 5
 5.
 92
 0.
 84
 0.
 27
 ,1
 .9
 7
 17
 20
 .5
 3
 0.
 83
 0.
 48
 ,1
 .3
 3
 20
 to
 35
 km
 6
 4.
 72
 1.
 27
 0.
 47
 ,2
 .7
 7
 3
 2.
 70
 1.
 11
 0.
 23
 ,3
 .2
 5
 2
 2.
 40
 0.
 83
 0.
 10
 ,3
 .0
 1
 5
 4.
 28
 1.
 17
 0.
 38
 ,2
 .7
 3
 16
 14
 .1
 0
 1.
 13
 0.
 65
 ,1
 .8
 4
 en
 ti
 re
 st
 ud
 y
 zo
 ne
 :0
 to
 35
 km
 11
 13
 .2
 2
 0.
 83
 0.
 42
 ,1
 .4
 9
 9
 7.
 02
 1.
 28
 0.
 59
 ,2
 .4
 3
 7
 5.
 87
 1.
 19
 0.
 48
 ,2
 .4
 6
 11
 10
 .8
 2
 1.
 02
 0.
 51
 ,1
 .8
 2
 38
 36
 .9
 3
 1.
 03
 0.
 73
 ,1
 .4
 1
 10
 to
 20
 km
 in
 cl
 ud
 in
 g
 A
 ld
 er
 ne
 y
 4
 7.
 79
 0.
 51
 0.
 14
 ,1
 .3
 1
 3
 3.
 91
 0.
 77
 0.
 16
 ,2
 .2
 4
 5
 3.
 15
 1.
 59
 0.
 52
 ,3
 .7
 0
 5
 6.
 02
 0.
 83
 0.
 27
 ,1
 .9
 4
 17
 20
 .6
 8
 0.
 81
 0.
 48
 ,1
 .3
 2
 *On
 e
 tail
 ,97.5
 %
 confidenc
 e
 inte
 rv
 al
 s.
 Childhood leukaemia around nuclear sites 471
 www.jech.com
Bloom syndrome, ataxia telangiectasia, Fan-
 coni anaemia, Li-Fraumeni or immuno-
 deficiency syndromes.
 The expected total number of cases in the
 study area was 36.93, and 38 cases were
 observed (SIR=1.03; 95%CI: 0.73, 1.41)
 (table 4). In the 0 to 10 km zone (Beaumont-
 Hague), there were five cases whereas 2.30
 were expected. The SIR for the entire 0 to 24
 year old group was 2.17 (95%CI: 0.71, 5.07).
 The highest SIR for an age group was for the 5
 to 9 year olds: there were three cases observed
 in this group although 0.47 were expected
 (SIR=6.38; 95%CI: 1.32, 18.65). There was
 no excess in number of cases for the 10 to 35
 km zones for any sex or age group. In the 0 to
 24 year old population of Alderney, there were
 no cases of leukaemia.
 Table 5 shows the results classified according
 to type of leukaemia (acute lymphoblastic leu-
 kaemia and acute myeloblastic leukaemia) for
 children under the age of 15. The SIR was 5.77
 for acute lymphoblastic leukaemia in the 5 to 9
 year old age group (95%CI: 1.19, 16.86). All
 three cases involved were boys born in the
 ?d?partement? of La Manche. These cases
 were diagnosed in 1981, 1989 and 1998.
 Discussion
 For the area studied as a whole, the number of
 cases observed was consistent with the number
 expected. When comparing the three areas
 around the La Hague plant, the highest SIR of
 leukaemia among people aged less than 25
 years was observed in the 0 to 10 km area
 (SIR=2.17; 95%CI: 0.71, 5.07). In this zone,
 the highest SIR concerned the 5 to 9 year olds.
 These cases were three children aged 5 or 6 and
 suVering acute lymphoblastic leukaemia.
 Of the 194 doctors practising in the area at
 some time during the study period, nine
 (4.6%) were dead, four (2.1%) could not be
 traced, and 23 (11.9%) did not reply. The
 highest response rates were in the zones less
 than 10 km and 10 to 20 km from the plant
 (83.3% and 86.7% respectively). The response
 rate was 76.9% for the 20 to 35 km zone and
 73.7% for the surrounding area, and these
 relatively low response rates raise the possibility
 of underascertainment of cases in these areas.
 It is likely, in any event, that physicians with no
 cases to report would tend to be found among
 the non-responders. The files of the usual
 healthcare system were used, as far as possible,
 to validate the data, but are not exhaustive for
 the earlier part of the period under study. All
 the diagnoses were validated by the same
 investigator who had no information about the
 patient (sex, age or place of residence).
 In France, general population cancer regis-
 ters cover the population of a ?d?partement?,
 with the consequence that the population sizes
 are small. The reference values used were
 calculated by combining data from registers
 from five ?d?partements? in which the inci-
 dence rates of cancer are stable over time.
 There are also three registers in France record-
 ing paediatric cancer (under 15 years old).
 According to these paediatric registers, the
 expected number of cases in the under 15 year
 old group in our study is 32.42, and 27 were
 observed (SIR=0.83; 95%CI: 0.55, 1.21).
 Using these registers for reference, the SIR in
 the Beaumont-Hague electoral ward in 5 to 9
 year old group is smaller (SIR=4.62; 95%CI:
 0.95, 13.49; 0.65 expected cases). Because of a
 more accurate data collection, the paediatric
 registers give reference incidence rates higher
 than those from general population registers.
 Indeed, the expected number of cases of acute
 lymphoblastic leukaemia in the 5 to 9 year old
 group calculated from the paediatric registers
 is higher than the expected numbers in the
 same age group of all forms of leukaemia
 calculated from the general population regis-
 ters.
 Linear interpolations between census dates
 provide an inaccurate estimate of the popula-
 tion because there was substantial migration to
 and from the study region. During the study
 period, there were two major building projects
 in the Nord Cotentin region: the nuclear power
 station at Flamanville (1978 to 1986) and the
 construction of a new nuclear waste reprocess-
 ing unit on the La Hague site (1982 to 1991).
 The diagonal interpolation method we used
 takes account of the aging of the population
 and of the numbers of births and deaths.15 The
 methodological options taken for both the esti-
 mation of the at risk population and the refer-
 ence incidence rate explained the higher
 expected number obtained in this study as
 compared with the previous ones.6 7
 Acute lymphoblastic leukaemias are the
 most prevalent forms of leukaemia among
 those under 15 years old, and account for the
 peak in leukaemia incidence observed in young
 children in industrialised countries.22 In our
 study, there were four cases of acute lympho-
 blastic leukaemia in 1 to 6 year olds in
 Beaumont-Hague, whereas the number ex-
 pected from the Lorraine paediatric register is
 Table 5 Numbers of observed (O) and expected (E) cases of acute lymphoblastic leukaemia (ALL) by five year age group, and of acute myeloblastic
 leukaemia (AML) in the 0 to 14 year old group (reference incidence rates from the paediatric registers of Lorraine and Provence-Alpes-C?tes-d?Azur and
 Corsica regions)
 Zones
 Cytological type and age (y)
 ALL, 0 to 4 ALL, 5 to 9 ALL, 10 to 14 ALL, 0 to 14 AML,0 to 14
 O E SIR 95% CI O E SIR 95% CI O E SIR 95% CI O E SIR 95% CI O E SIR 95% CI
 0 to 10 km 1 0.89 1.12 0.03, 6.26 3 0.52 5.77 1.19, 16.86 0 0.25 0.00 0.00, 14.75* 4 1.66 2.41 0.66, 6.17 0 0.27 0.00 0.00, 13.66*
 10 to 20 km 3 8.24 0.36 0.08, 1.06 2 4.28 0.47 0.06, 1.69 3 2.03 1.48 0.30, 4.32 8 14.55 0.55 0.24, 1.08 4 2.36 1.70 0.46, 4.34
 20 to 35 km 4 5.06 0.79 0.22, 2.02 3 3.01 1.00 0.21, 2.91 2 1.58 1.27 0.15, 4.57 9 9.65 0.93 0.43, 1.77 1 1.60 0.63 0.02, 3.48
 entire study zone:
 0 to 35 km 8 14.19 0.56 0.24, 1.11 8 7.81 1.02 0.44, 2.02 5 3.86 1.30 0.42, 3.02 21 25.86 0.81 0.50, 1.24 5 4.24 1.18 0.38, 2.75
 *One tail, 97.5% confidence intervals.
 472 Guizard, Boutou, Pottier, et al
 www.jech.com
0.96 (SIR=4.17; 95%CI: 1.14, 10.67).20 The
 incidence of acute myeloblastic leukaemia is
 more regular during childhood. These observa-
 tions motivated our detailed analysis of cyto-
 logical types of leukaemia. In Beaumont-
 Hague, the excess number of cases of
 leukaemia seems to be entirely due to the 2.48
 excess cases of acute lymphoblastic leukaemia
 in the 5 to 9 year old group. For the 1 to 6 year
 old group, the excess was 3.04 over a period of
 21 years. For acute myeloblastic leukaemia, the
 number of cases was insuYcient to detect any
 excess.
 Although the La Hague plant began its
 reprocessing activities in 1966, it was techni-
 cally impossible to reconstruct the incidence of
 childhood leukaemia before 1978. A mortality
 study had been conducted for the years 1968 to
 1978.5 For the overall Nord Cotentin area, no
 excess mortality was observed with no death
 from leukaemia in the Beaumont-Hague elec-
 toral ward. Although mortality is a crude indi-
 cator of morbidity for childhood leukaemia,
 this result may indicate that nothing dramatic
 occurred around La Hague in the period prior
 to 1978, when the site was operational.
 There have been three previous studies of
 the incidence of leukaemia in the neighbour-
 hood of La Hague for the periods 1978?90,6
 1978?92,7 and 1978?1996.25 Though these
 suggested a small excess of childhood leukae-
 mia in comparison with expected, the numbers
 in each study were very small, and the results
 therefore somewhat equivocal, leading to the
 conclusion that it was important that the situa-
 tion be kept under review. This is the major
 reason for this study. All cases diagnosed before
 1997 (table 3) had already been included in
 previous analyses. The period 1993?1998 is
 too short to be analysed separately from the
 period 1978 to 1992, especially when consider-
 ing detailed age classes and cytological types of
 leukaemia. Adding this period confirmed that
 the incidence of leukaemia in young people in
 the Beaumont-Hague electoral ward was quite
 high (SIR=2.17) and showed that it consisted
 mainly in acute lymphoblastic leukaemia oc-
 curring during the childhood incidence peak.
 Our data have already been partially ana-
 lysed, which increases the risk of erroneously
 concluding that there is an excess. Multiple
 comparisons performed by age, zone and,
 cytological type could give rise to at least one
 significant result by chance alone. In these cir-
 cumstances, the type I error is not controlled
 anymore and confidence limits should be
 regarded only as numerical indices providing
 guidance for further research. Our findings are
 consistent with those in similar circumstances:
 near Dounreay where the SIR is 3.3,26 and at
 Seascale where the SIR is 10.2.1
 Several possibilities have been suggested to
 explain the excess number of cases of leukae-
 mia observed around nuclear reprocessing
 plants. They include paternal exposure to
 radioactivity prior to conception,27 environ-
 mental exposure to radioactivity,8 and popula-
 tion movements.28 As the results of the
 case-control study by Gardner et al had never
 been reproduced, the hypothesis of paternal
 preconceptional exposure to ionising radiation
 was dismissed.29 Moreover, the case-control
 study by Pobel and Viel was not in favour of
 this hypothesis.8
 A study of environmental radiation con-
 cluded that it is very unlikely that exposure to
 radioactive discharge from the nuclear installa-
 tions in Nord Cotentin could cause a detect-
 able increase in the incidence of leukaemia in
 Beaumont-Hague30: of the four cases observed
 from 1978 to 1996, 0.83 could be attributed to
 ionising radiation, including only 0.0015 due
 to radioactive discharge from the various
 nuclear installations in Nord Cotentin. Al-
 though the results seemed robust, they corres-
 pond to an average estimation and some
 reserves have been expressed about the lack of
 an uncertainty analysis. Genetic susceptibility
 has been evoked as an eVect modifier that
 could potentiate the eVect of ionising radia-
 tion.31
 Dickinson and Parker recently quantified the
 association between the occurrence of child-
 hood leukaemia and non-Hodgkin?s
 lymphoma, and population mixing among
 children born in Cumbria.23 The association
 was all the more stronger when acute lympho-
 blastic leukaemia among children aged 1 to 6
 years were examined. Our study indicates the
 predominance of acute lymphoblastic leukae-
 mia over childhood leukaemia cases diagnosed
 in the Beaumont-Hague electoral ward. Al-
 though not conclusive, this observation could
 be linked to the dramatic intensity of popula-
 tion movement that occurred in this particular
 area. A study is currently underway to analyse
 population movement and childhood leukae-
 mia in Nord Cotentin. Indeed, it currently
 seems diYcult to dissociate the correlation
 between the incidence of leukaemia and prox-
 imity to the plant from that between leukaemia
 and population movements.
 Several diseases increase the risk of leukae-
 mia.32 33 Individuals with Down?s syndrome
 have a 10-fold to 18-fold increased for leukae-
 mia, FAB M7 megacaryoblastic subtype before
 3 years and acute lymphoblastic leukaemia
 after 3 years of age.32 In our study, three
 patients suVered Down?s syndrome and devel-
 oped acute leukaemia: two of them were acute
 lymphoblastic leukaemia, the third one could
 not be characterised. It could have been inter-
 esting to produce the analysis without cases
 KEY POINTS
 x Surveillance of childhood and young
 adulthood leukaemia around the La
 Hague nuclear waste reprocessing plant
 continued until 1998.
 x An increased incidence of leukaemia is
 reported in the 5 to 9 years age group in
 the nearest area from the site.
 x Analysis of cytological type shows that
 this increased incidence could be attribut-
 able mostly to acute lymphoblastic leu-
 kaemia.
 x No cases were observed on Alderney
 from 1978 to 1998.
 Childhood leukaemia around nuclear sites 473
 www.jech.com
suVering Down?s syndrome. However, leukae-
 mia reference incidence rates excluding pa-
 tients with Down?s syndrome are not available
 in France. Moreover, no patient with Down?s
 syndrome was living in the Beaumont-Hague
 electoral ward when diagnosed. Exclusion of
 patients with Down?s syndrome from the
 analysis could increase the SIR in this particu-
 lar area. The 35 other patients presented no
 clinical or history evidence for trisomy 8
 syndrome, Bloom syndrome, ataxia tel-
 angiectasia, Fanconi anaemia, Li-Fraumeni or
 immunodeficiency syndromes. Neither was a
 pure familial leukaemia observed in these
 patients.
 In view of statistically significant clusters of
 childhood leukaemia near other European
 nuclear reprocessing sites, and the concerns of
 the local population, these findings argue in
 favour of continued investigations in Nord
 Cotentin. Three lines should be followed:
 measuring the incidence of child leukaemia
 among people who have lived at any time in
 Beaumont-Hague; identifying possible causes
 of leukaemia in the area (studies of population
 movements); and measuring the incidence of
 other diseases the occurrence of which could
 be linked to radiation (other cancers, and
 reproductive function disorders).
 We thank the general practitioners and paediatricians of the
 study area; Dr M Barre, ?d?partement d?Information M?di-
 cale?, Pasteur Hospital, Cherbourg; Dr Bienvenu, Department
 of Medicine, General Hospital, Valognes; Dr P Boutard, Paedi-
 atric Oncology Unit, University Hospital, Caen; Dr Cau, Paedi-
 atric Department, Pasteur Hospital, Cherbourg; Dr Cooper, St
 Anne?s, Alderney; Dr M Henry-Amar, Regional Cancer
 Institute, Caen; Dr D JeVs, Director of Public Health,
 Guernsey; Pr M Leporrier, Department of Haematology,
 University Hospital, Caen; Dr J-F Leseven, Laboratory of Biol-
 ogy, Pasteur Hospital, Cherbourg; Dr M Malet, Laboratory of
 Haematology, University Hospital, Caen; Mrs J Mace, Regional
 Cancer Institute, Caen; Dominique Mouchel, ARKM; Dr Jean-
 Luc Mouchel, ARKM; Dr Quanten, St Anne?s, Alderney; Dr
 Rouby, Laboratory of Biology, Lebas Hospital, Cherbourg; Dr
 Stefani, chairman of the ?Conseil d?partemental de l?ordre des
 m?decins?; Dr Stocker, St Anne?s, Alderney.
 Funding: this study was supported by a grant from ?Institut
 National de la Veille Sanitaire? (InVS), St Maurice, France, by
 the ?Direction G?n?rale de la Sant??, Paris, France, contract
 no: 10/2436 and by the ?Conseil r?gional de Basse-
 Normandie?, Caen, France, convention no 8-A-6, ?F?d?ration
 des registres de Basse-Normandie?.
 Conflicts of interest: ARKM is partly funded by COGEMA
 (7.4% of the annual budget), owner and operator of the La
 Hague nuclear waste reprocessing plant.
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