Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project

Alexander, FE; Boyle, P.; Carli, P. M.; Coebergh, Jan Willem; Draper, G J; Ekbom, Anders; Levi, Fabio; McKinney, P A; McWhirter, W.; Michaelis, J; Peris-Bonet, Rafael; Petridou, Eleni; Pompe-Kirn, Vera; Plisko, I.; Pukkala, Eero; Rahu, Mati; Storm, Hans H.; Terracini, Benedetto; Vatten, L; Wray, Naomi R.

doi:10.1038/bjc.1998.133

Cited by 65 publications

(57 citation statements)

References 25 publications

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“…A small number of countries have a deficit of space-time pairs; these include Germany and Sweden for series Al and Norway for series A2. Excess space-time pairs are seen for countries that did not show evidence of generalized clustering (Alexander et al, 1998) as well as those that did.…”

Section: Resultsmentioning

confidence: 91%

“…The primary objective was to determine whether the disease showed a general tendency to cluster within small areas. The results (Alexander et al, 1998) show statistically significant evidence of clustering, although the magnitude is small. The only previous investigation of spatial clustering of childhood leukaemia (CL) in a large dataset was conducted in the UK (Draper, 1990 (1993) and Kinlen (1995).…”

mentioning

confidence: 76%

“…Thus, the prevailing hypotheses for infant leukaemia, unlike those for older cases, do not relate to exposure to infectious agents. However, as the statistical significance of the EUROCLUS results depended on the inclusion of the infant cases (Alexander et al, 1998) the analyses were extended to include infants.…”

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confidence: 99%

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Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin

Alexander

Boyle²,

Carli³

et al. 1998

Br J Cancer

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Summary The EUROCLUS project included information on residence at diagnosis for 13 351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P = 0.0002) and 26% (P = 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia.Keywords: infection; childhood leukaemia; acute lymphoblastic leukaemia; delayed exposure; infant leukaemia; in utero exposure; cluster Leukaemia is the most frequent childhood malignancy (Parkin et al, 1988), but the cause of the majority of cases remains unknown (Doll, 1989). Reports of clusters of leukaemia, usually involving children, have been frequent throughout this century (Alexander, 1993), but their aetiological significance remains obscure. The EUROCLUS project was established to investigate the geographical pattern of the disease using specialist registry data from a wide spectrum of European countries, and also from Queensland, Australia. The primary objective was to determine whether the disease showed a general tendency to cluster within small areas. The results (Alexander et al, 1998) show statistically significant evidence of clustering, although the magnitude is small. The only previous investigation of spatial clustering of childhood leukaemia (CL) in a large dataset was conducted in the UK (Draper, 1990 (1993) and Kinlen (1995). A second objective of EUROCLUS was to test these hypotheses and make comparisons with the results of the UK analysis (Alexander, 1992). Specific subgroups of interest are (a) cases of acute lymphoblastic leukaemia (ALL) in the childhood peak, and (b) cases of CL aged 5-14 years. Critical times, specified in advance are for (a) the 18-month period preceding diagnosis, and for (b), 1 year before to 1 year after birth.A third subgroup of interest that had not been included in the UK analysis is infant leukaemia (diagnosed < 1 year or < 18 months), which has recently emerged as an interesting biological entity as a large...

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Section: Resultsmentioning

confidence: 91%

mentioning

confidence: 76%

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Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin

Alexander

Boyle²,

Carli³

et al. 1998

Br J Cancer

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“…Properties of rural areas include low population density, relative isolation, limited commuting or visitation from other areas, etc, although specific definitions vary by county. Others have explored the use of population density as the predictor of high cancer rates (rather than population mixing) with somewhat mixed results (Alexander et al, 1990(Alexander et al, , 1998b(Alexander et al, , 1999Ross et al, 1999). One recent paper provided somewhat contradictory results, showing that increased risk of childhood leukaemia associated with inward migration was more marked in urban than rural areas (Dickinson et al, 2002a).…”

Section: Discussionmentioning

confidence: 99%

Childhood leukaemia incidence and the population mixing hypothesis in US SEER data

Wartenberg¹,

Schneider

Brown

2004

Br J Cancer

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We evaluated the infectious aetiology hypothesis of childhood leukaemia that rapid population influx into rural areas is associated with increased risk. Using data from the US SEER program, we found that in changes in rural county population sizes from 1980 to 1989 were associated with incidence rates for childhood acute lymphocytic leukaemia (ALL). The observed associations were strongest among children 0 -4 years of age, born in the same state as diagnosis, in extremely rural counties, and when counties adjacent to nonrural counties were excluded. Similar analyses for brain and central nervous system (CNS) cancer in children, a disease less linked to this infectious hypothesis, provide evidence against methodologic bias. Similar evaluations for other decades were not meaningful due to limited sample sizes and, perhaps, increased population mobility.

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“…L'objectif de ces études est de déterminer si la distribution spatiale des leucémies est aléatoire (suivant une loi de Poisson) ou si les leucémies présentent une tendance à l'agrégation spatiale (Alexander and Cuzick, 1996;Gilman and Knox, 1995 ;Muirhead and Butland, 1996 ;Petridou et al, 1997 ;Westermeier and Michaelis, 1995). Si quelques études ont conclu à l'absence d'agrégats de leucémies (Cartwright et al, 1990;Westermeier and Michaelis, 1995), la plupart concluent à l'existence d'une tendance <<naturelle >> à l'agrégation des cas de leucémie, (Alexander et al, 1998;Gilman and Knox, 1995;Petridou et al, 1997). La confirmation de l'existence d'une tendance naturelle à l'agrégation des leucé-mies remettrait en cause la validité des tests utilisés pour juger de l'existence d'un excès de cas autour d'un point donné (reposant sur l'hypothèse d'une distribution poissonniène des cas de leucémie).…”

Section: Limites Des éTudes De Clusterunclassified

Leucémies chez les moins de 25 ans autour d'installations nucléaires en France et à létranger : revue des études épidémiologiques descriptives

Laurier

1999

Radioprotection

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Bases des études épidémiologiques descriptives Mesure de l a fréquence des leucémiesLa fréquence des leucémies peut être quantifiée à partir, soit du nombre de décès (études de mortalité), soit du nombre de diagnostics (études d'incidence). Les études d'incidence sont a priori plus intéressantes pour trois raisons : (i) le taux de rémis-sion des leucémies aiguës chez les enfants est aujourd'hui de près de 75 % (Liesner and Goldstone, 1997), (ii) les taux de mortalité montrent une forte décroissance dans le temps (Hill et al., 1989 ;1993), (iii) la détermination du type de leucémie est imprécise dans les certificats de décès (en France par exemple, près d'un tiers des décès par leucémie sont sans type précisé).

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Spatial clustering of childhood leukaemia: summary results from the EUROCLUS project

Cited by 65 publications

References 25 publications

Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin

Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin

Childhood leukaemia incidence and the population mixing hypothesis in US SEER data

Leucémies chez les moins de 25 ans autour d'installations nucléaires en France et à létranger : revue des études épidémiologiques descriptives

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