Summary The interpretation of reports of clusters of childhood leukaemia is difficult, first because little is known about the causes of the disease, and second because there is insufficient information on whether cases show a generalized tendency to cluster geographically. The EUROCLUS project is a European collaborative study whose primary objective is to determine whether the residence locations of cases at diagnosis show a general tendency towards spatial clustering. The second objective is to interpret any patterns observed and, in particular, to see if clustering can be explained in terms of either infectious agents or environmental hazards as aetiological agents. The spatial distribution of 13 351 cases of childhood leukaemia diagnosed in 17 countries between 1980 and 1989 has been analysed using the Potthoff-Whittinghill method. The overall results show statistically significant evidence of clustering of total childhood leukaemia within small census areas (P= 0.03) but the magnitude of the clustering is small (extra-Poisson component of variance (%) = 1.7 with 90% confidence interval 0.2-3.1). The clustering is most marked in areas that have intermediate population density (150-499 persons km-2). It cannot be attributed to any specific age group at diagnosis or cell type and involves spatial aggregation of cases of different ages and cell types. The results indicate that intense clusters are a rare phenomenon that merit careful investigation, although aetiological insights are more likely to come from investigation of large numbers of cases. We present a method for detecting clustering that is simple and readily available to cancer registries and similar groups.

The causes of cutaneous melanoma among children under 15 years are largely unknown. We report the findings of an epidemiological study of childhood melanoma in Queensland, Australia, which has the highest incidence rates in the world. All 61 cases of melanoma in children less than 15 years notified to the Queensland Cancer Registry 1987-1994 were eligible to participate in a population-based, case-control study. Data were collected through structured, face-to-face interviews with parents and skin examinations of the 52 participating cases and 156 age-and sex-matched controls. The strongest determinants of melanoma risk found among Queensland children were constitutional factors, including the presence of more than 10 naevi greater than 5 mm in diameter (RR 9.9, 95% CI 2.5-38.9), heavy facial freckling (RR 6.4, 95% CI 1.9-21.6), an inability to tan on exposure to the sun (RR 8.8, 95% CI 2.1-36.2) and a family history of melanoma (RR 4.2, 95% CI 1.9-9.3). These factors remained significantly associated with melanoma after adjusting for other risk factors. No measures of acute or chronic exposure to solar UV radiation were associated with childhood melanoma in our study. Established risk factors, including giant congenital naevi and xeroderma pigmentosum, were not present among any of the children in the study. Melanoma in childhood appears to have similar epidemiologic characteristics to the adult form of the disease, being associated with a cluster of phenotypic attributes indicating cutaneous sensitivity to the effects of sun exposure. Our findings support the contention that childhood melanoma occurs in susceptible individuals with a low threshold for pigment cell tumorigenesis. From a public-health perspective, children at elevated risk for melanoma can be identified on the basis of phenotype and family history. Int.

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...

The incidence of cutaneous melanoma in children aged 0-14 years was examined in Queensland, Australia. Details of notifications were collected from the population-based Australian Paediatric Cancer Registry. Between 1987 and 1994, the age-adjusted incidence rates of invasive cutaneous melanoma occurring in Queensland children were estimated at 8.5/million for males and 7.1/million for females. Incidence rates rose steeply in both sexes with increasing age, from less than 1/million in the 0-4 age group, to nearly 30/million in the 10-14 age group. To assess the uniformity of the anatomical distribution of lesions, relative tumour densities (RTDs) were calculated compared with the body as a whole. In both sexes, melanomas were most common on the trunk (RTD> 3), while lower limb lesions were less common (RTD < 0.6) and no melanomas were reported on the buttocks or external genitalia. Although not statistically significant, there was a tendency for truncal lesions in males to occur on the back, while in females, truncal melanomas were more evenly distributed across the chest, back and shoulders. No consistent relationship between latitude and melanoma incidence was observed, with higher rates reported in the subtropical than the tropical regions of Queensland. These are the first reported incidence rates of cutaneous melanoma in Australian children and are the highest ever reported in the world in this age group. Our findings provide baseline data from which to monitor changes in the occurrence of cutaneous melanoma in children.

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