Article Text

A negative association between Down’s syndrome and neuroblastoma
  1. DANIEL SATGE
  1. Laboratoire d’Anatomie Pathologique
  2. Centre Hospitalier 19000 Tulle
  3. France
  4. Program of Epidemiology for Cancer Prevention
  5. International Agency for Research on Cancer
  6. 150 cours Albert Thomas, 69372 Lyon Cedex 08 and
  7. Institut National de la Sante et de la Recherche Medicale (INSERM)
  8. France
  9. Odense Universitethospital
  10. DK–5000 Odense
  11. Denmark
  12. Medecine Infantile B CHU Purpan
  13. 31059 Toulouse Cedex
  14. France
  15. Childhood Cancer Research Group
  16. University of Oxford
  17. Department of Paediatrics
  18. Oxford OX2 6HJ
    1. ANNIE J SASCO
    1. Laboratoire d’Anatomie Pathologique
    2. Centre Hospitalier 19000 Tulle
    3. France
    4. Program of Epidemiology for Cancer Prevention
    5. International Agency for Research on Cancer
    6. 150 cours Albert Thomas, 69372 Lyon Cedex 08 and
    7. Institut National de la Sante et de la Recherche Medicale (INSERM)
    8. France
    9. Odense Universitethospital
    10. DK–5000 Odense
    11. Denmark
    12. Medecine Infantile B CHU Purpan
    13. 31059 Toulouse Cedex
    14. France
    15. Childhood Cancer Research Group
    16. University of Oxford
    17. Department of Paediatrics
    18. Oxford OX2 6HJ
      1. NIELS L T CARLSEN
      1. Laboratoire d’Anatomie Pathologique
      2. Centre Hospitalier 19000 Tulle
      3. France
      4. Program of Epidemiology for Cancer Prevention
      5. International Agency for Research on Cancer
      6. 150 cours Albert Thomas, 69372 Lyon Cedex 08 and
      7. Institut National de la Sante et de la Recherche Medicale (INSERM)
      8. France
      9. Odense Universitethospital
      10. DK–5000 Odense
      11. Denmark
      12. Medecine Infantile B CHU Purpan
      13. 31059 Toulouse Cedex
      14. France
      15. Childhood Cancer Research Group
      16. University of Oxford
      17. Department of Paediatrics
      18. Oxford OX2 6HJ
        1. HERVE RUBIE
        1. Laboratoire d’Anatomie Pathologique
        2. Centre Hospitalier 19000 Tulle
        3. France
        4. Program of Epidemiology for Cancer Prevention
        5. International Agency for Research on Cancer
        6. 150 cours Albert Thomas, 69372 Lyon Cedex 08 and
        7. Institut National de la Sante et de la Recherche Medicale (INSERM)
        8. France
        9. Odense Universitethospital
        10. DK–5000 Odense
        11. Denmark
        12. Medecine Infantile B CHU Purpan
        13. 31059 Toulouse Cedex
        14. France
        15. Childhood Cancer Research Group
        16. University of Oxford
        17. Department of Paediatrics
        18. Oxford OX2 6HJ
          1. CHARLES A STILLER
          1. Laboratoire d’Anatomie Pathologique
          2. Centre Hospitalier 19000 Tulle
          3. France
          4. Program of Epidemiology for Cancer Prevention
          5. International Agency for Research on Cancer
          6. 150 cours Albert Thomas, 69372 Lyon Cedex 08 and
          7. Institut National de la Sante et de la Recherche Medicale (INSERM)
          8. France
          9. Odense Universitethospital
          10. DK–5000 Odense
          11. Denmark
          12. Medecine Infantile B CHU Purpan
          13. 31059 Toulouse Cedex
          14. France
          15. Childhood Cancer Research Group
          16. University of Oxford
          17. Department of Paediatrics
          18. Oxford OX2 6HJ

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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.

            Acknowledgments

            A grant from ‘Ligue pour la Lutte Contre le Cancer’ Tulle, Correze, France supported this study.

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