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Keywords:

  • familial risks;
  • ganglioneuroma;
  • genetic factors;
  • neuroblastoma;
  • penetrance

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.