Genetic epidemiology of neuroblastoma: A study of 426 cases at the Institut Gustave-Roussy in France

Authors

  • Taraneh Shojaei-Brosseau MD,

    1. Unité de Recherches en Epidémiologie des Cancers INSERM U521, Institut Gustave Roussy, Villejuif Cedex, France
    Current affiliation:
    1. INSERM EMI 00-06, Tour Evry 2, 523 Place des Terrasses de l'Agora, 91034 Evry Cedex, France.
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  • Agnès Chompret MD,

    Corresponding author
    1. Unité de Recherches en Epidémiologie des Cancers INSERM U521, Institut Gustave Roussy, Villejuif Cedex, France
    2. Département d'Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif Cedex, France
    • Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
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  • Anne Abel MD,

    1. Unité de Recherches en Epidémiologie des Cancers INSERM U521, Institut Gustave Roussy, Villejuif Cedex, France
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  • Florent de Vathaire PhD,

    1. Unité de Recherches en Epidémiologie des Cancers INSERM U521, Institut Gustave Roussy, Villejuif Cedex, France
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  • Marie-Anne Raquin MD,

    1. Département d'Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif Cedex, France
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  • Laurence Brugières MD,

    1. Département d'Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif Cedex, France
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  • Jean Feunteun PhD,

    1. Laboratoire de Génétique Oncologique, CNRS UMR #1599, Institut Gustave Roussy, Villejuif Cedex, France
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  • Olivier Hartmann MD,

    1. Département d'Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif Cedex, France
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  • Catherine Bonaïti-Pellié MD, PhD

    1. Unité de Recherches en Epidémiologie des Cancers INSERM U521, Institut Gustave Roussy, Villejuif Cedex, France
    Current affiliation:
    1. INSERM U535, Bâtiment Gregory Pincus, CHU de Bicêtre, 80 rue du général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.
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  • This manuscript was originally submitted to and accepted for publication in Medical & Pediatric Oncology by its Editor-in-Chief, Dr. G. D'Angio.

Abstract

Background

Genetic susceptibility to neuroblastoma (NB) is now highly probable and the likelihood that it may also confer a higher risk of other cancer types has been suggested. The aim of this study was to estimate the fraction of inherited cases and penetrance associated with a carrier status, and to investigate the hypothesis that susceptibility cancer genes might be non-specific.

Procedure

The family history of 426 children treated for NB at the Institut Gustave Roussy was obtained. The excess of relatives affected by NB or early-onset cancer (EOC) was sought using the standardized incidence ratio (SIR). The risk of NB among sibs was estimated taking into account the age of patients' sibs. Estimation of penetrance in hereditary cases and of the proportion of sporadic cases was obtained using segregation analysis of proband sibships.

Results

There was a positive family history of NB or ganglioneuroma in 5 of the 426 cases (1.2%). A highly significant excess of NB was found among relatives (SIR = 11.4, 95% CI: 3.7–26.5). The excess of EOC (SIR = 1.22, 95% CI = 0.92–1.58) was non-significant, but it was of borderline significance among first-degree relatives (SIR = 1.70, 95% CI = 0.99–2.72). The risk of NB among sibs was estimated at 0.2% (95% CI = 0.004–1.0%). Penetrance in hereditary cases was estimated at 11.4% and the proportion of inherited cases, 3.5%.

Conclusions

The genetic factors heightening susceptibility to NB are most probably dominantly inherited with low penetrance and are involved in only a very small fraction of NB patients. The overall risk in sibs is very low and this should reassure parents with regard to their other children. We found some arguments for the existence of non-specific genetic susceptibility, which would slightly in crease the probability of developing any cancer. © 2003 Wiley-Liss, Inc.

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