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Editor,—Only one ganglioneuroma and a poorly documentated case of neuroblastoma associated with Down’s syndrome have ever been published.1 In order to obtain population based data an epidemiological study was conducted in seven European countries, five with specialised registries (Denmark, Germany, Great Britain, Italy, Switzerland), one with four regional registries (Netherlands), and one with centralised registration of treatment of children with neuroblastoma (France), covering the whole population to verify if neuroblastomas are under-represented in Down’s syndrome.
In a total of 6484 cases of neuroblastomas, there were no cases of Down’s syndrome. Taking the general prevalence of Down’s syndrome at birth as 12/10 000 live births and the life expectancy at 15 years for the syndrome as 76%, but making no allowance for the predominantly young age of children with neuroblastoma, 5.91 cases would be expected. The Poisson probability of no cases is 0.0027, strongly suggesting a reduced risk of neuroblastoma in Down’s syndrome, probably specific because other neoplasms, particularly leukaemias, lymphomas, and testicular and extragonadal germ cell, and perhaps bone and pancreatic tumours, are seen in excess in Down’s syndrome.2 This result could be linked to the hypoplasia of the sympathetic nervous system and particularly of the adrenal medulla observed in those with Down’s syndrome.
A proposed mechanism for both phenomena could be related to the overproduction of S-100 b protein by gene dosage effect both prenatally and after birth, the gene of which is situated on the long arm of chromosome 21. This protein expressed in utero induces neural differentiation in vitro and is in excess in blood, cerebral fluid, and nervous tissues in Down’s syndrome both prenatally and after birth. S-100 protein is abundant in the stroma of neuroblastomas with good prognosis and absent in neuroblastomas with poor outcome. In vitro, it specifically inhibits the growth of different human and murine cell lines of neuroblastoma (personal data, D Satge).3 Although several genetic disorders such as Von Recklinghausen’s disease, Hirschsprung’s disease, Wiedeman-Beckwith syndrome, Turner’s syndrome, Duchenne muscular dystrophy, and cystic fibrosis have been described in association with neuroblastoma no definite relationship between a higher risk of neuroblastoma and a specific genetic disease is proved.4 Furthermore, as far as we know a decreased incidence of a specific neoplasm in a particular genetic disease has not yet been reported. These arguments and data favour a protective effect of Down’s syndrome against emergence of neuroblastoma. They should be considered regarding both understanding of oncogenesis and treatment of neuroblastoma.
A grant from ‘Ligue pour la Lutte Contre le Cancer’ Tulle, Correze, France supported this study.