Malignant renal tumours incidence and survival in European children (1978–1997): Report from the Automated Childhood Cancer Information System project
Introduction
Malignant renal tumours comprise 6% of all childhood cancers, with Wilms’ tumour (WT) being the most frequent type (90%).1 The majority of WT are solitary lesions, but approximately 12% of children develop multifocal tumours within a single kidney and almost 7% have bilateral involvement at diagnosis or later on.2, 3 Children with unilateral tumours are older than cases with bilateral ones, in accordance with Knudson’s two hit hypothesis.4
WT occurs as part of several distinct congenital malformation syndromes. Overgrowth syndromes, in particular Beckwith–Wiedemann syndrome carry an approximately 5% risk of developing WT.2 Syndromes involving genitourinary anomalies combined with aniridia and variable mental retardation, or with nephrotic syndrome are associated with mutations of the WT1 gene on chromosome 11p13 and carry a greatly increased risk of developing WT.2 Children with these congenital abnormalities are at risk of bilateral kidney involvement.5 There is evidence for multiple WT predisposition genes. At least three susceptibility genes have been implicated in familial WT, which is found in 1–2% of cases.6 Epidemiological studies suggest that ethnicity affects the incidence rates more than geographical region of residence.1, 7 These observations, in addition to inconsistent results from case-control studies, suggest that environmental factors play a marginal role in the aetiology of this tumour.2, 7
Over the past 40 years, the prognosis of children with WT has improved due to risk-adapted use of an armamentarium of effective therapies. The development of treatment strategies for WT has been a paradigm for the contribution of randomised multicentre clinical trials to progress in paediatric oncology.3, 8, 9, 10
Clear cell sarcoma of the kidney (CCSK) is a rare childhood renal cancer. The clinical course is characterised by a wider spread of metastases to bone, brain and lungs, by a longer period at risk of relapse and by historically poorer outcome than WT.11
Rhabdoid tumour of the kidney (RTK) occurs mostly in infants. It is a highly aggressive entity, often with brain metastasis at diagnosis: the survival is less than 1 year from diagnosis for the majority of cases. It is associated with mutation of the INI1 gene on chromosome 22q in both renal and non-renal rhabdoid tumours, a mutation that is often constitutional.12
Renal cell carcinoma (RCC), the most common renal tumour in adults, is rare in childhood. Children are at risk of RCC when affected by Von Hippel–Lindau disease or tuberous sclerosis. A specific translocation at Xp11.2, characteristic of alveolar soft part sarcoma, has also been reported in papillary RCC diagnosed in younger children.13
International studies published to date reported incidence rates1, 14 and survival14, 15, 16 in Europe for the combined group of malignant renal tumours and for its three subgroups defined by the International Classification of Childhood Cancer.17 We present data from 59 population-based registries in Europe participating in ACCIS.18 In addition to a general overview of incidence and survival in Europe over the period 1978–1997 for the group of renal tumours, we also provide statistics for selected histological types; and compare data for unilateral versus bilateral Wilms’ tumours. Finally, we discuss the geographical and temporal variations of incidence and survival observed and propose future priorities for study of renal tumours within ACCIS.
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Material and methods
Children with malignant renal tumours diagnosed before the age of 15 years during the period 1978–1997 in 59 population-based cancer registries in 19 European countries were extracted from the ACCIS database and included in this study after a methodical evaluation of their quality and comparability.18 Table 1 shows the list of datasets included in the report, their grouping into geographical regions, the numbers of cases and the quality indicators. The very small number of cases registered from
Results
Data on 3134 newly diagnosed malignant renal tumours in children younger than 15 years of age during the period 1988–1997 were included in the incidence analysis. Table 3 presents the number of cases of renal tumour by histological subtype and age at diagnosis. The proportions of histological subtypes are shown in Fig. 1. WT (M-8960) was the most common type of renal tumour (93%). Over 77% were diagnosed in children before 5 years of age and 15% were diagnosed before the age of 1 year. The male
Discussion
The present study is the largest report of childhood renal tumours in Europe (over 5000 childhood renal tumour cases), focusing on incidence and survival data in the period 1988–1997, as well as on incidence and survival temporal patterns over the years 1978–1997.
Heterogeneity of contributions underlined selection of data sets for different analyses. The aim was to include the majority of available data in each type of analysis, (rather than restrict analyses to a smaller number of cancer
Conflict of interest statement
None declared.
Acknowledgements
The ACCIS project was funded by the European Commission in the framework of the Europe Against Cancer program (1996–2002) (agreements SI2.126875, SI2.321970 and SPC.2002303), jointly with International Agency for Research on Cancer (IARC). Data analyses were partly financed by the French Ligue National Contre le Cancer, Comité du Rhône. The activity of the Childhood Cancer Registry of Piedmont (CCRP) is supported by the Italian Association for Research on Cancer and by the Special Project
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These two authors equally contributed to this paper.