In developed countries, approximately 1 in 600 children develop cancer before they are 15 years old. Half of all childhood malignancies are diagnosed during the first 5 years of life. About 33% of cases are leukaemias, 25% brain tumours, and 10–12% lymphomas. The remaining cases are mainly embryonal tumours including neuroblastoma, Wilms’s tumour, embryonal rhabdomyosarcoma, retinoblastoma, and hepatoblastoma.1 2 Many of the leukaemias and brain tumours also constitute embryonal neoplasms. The histological appearance of embryonal neoplasms resembles that seen in the developing embryo and fetus. The early onset of these neoplasms and their embryonal appearance strongly suggest that prenatal, including genetic, factors are important. This article considers the role of genetic predisposition in the development of childhood cancer.

Genetic predisposition to cancer may be considered under four areas:

• highly penetrant genes that give rise to distinct familial clusters of cancers with a clear pattern of inheritance

• genes that confer a lower penetrance, with most gene carriers remaining unaffected. Multiple case familial clusters would not arise but occasional cancer affected sibling pairs or parent–child pairs may occur. Such genes may well exist and could play an important role in causing childhood cancers. At present, however, none has been identified and consequently, their possible importance cannot be estimated

• various syndromes that confer an increased risk of childhood cancers but where congenital abnormalities represent the main manifestation of the genetic disorder

• normal polymorphic variants of genes may exist that confer an increased risk of developing childhood cancers by modifying response to environmental factors.