دانلود کتاب سرطان در کودکان

The most obvious example of a genetically determined cancer is retinoblastoma; about 40% of cases have the heritable form of this disease. The pattern of inheritance is autosomal dominant, but in fact the gene RB1 is the first example of a tumour suppressor gene; about 90% of individuals who inherit the mutated form of this gene from a parent subsequently suffer a mutation of the wild- type (normal) allele, leading to loss of heterozygosity and the development of retinoblastoma. These individuals are also at increased risk of a variety of other cancers. Wilms tumour is associated with an especially wide range of syndromes and congenital anomalies, but the pattern of inheritance is more complicated and the proportion of clearly hereditary cases much smaller. Up to 10% of children and adolescents with cancer may have germline mutations in cancer predisposition genes. Other heritable syndromes carrying an increased risk of childhood cancer include neurofibromatosis types 1 and 2, tuberous sclerosis complex, Fanconi anaemia, ataxia telangiectasia, Li- Fraumeni syndrome, constitutional mismatch repair deficiency, xeroderma pigmentosum, and Bloom syndrome. There are also well- documented associations with chromosomal abnormalities; the strongest association is with Down syndrome, which occurs in a small percentage of cases of childhood leukaemia. If one child in a family has malignant disease, then, in the absence of any further information about the existence of genetic disease in that family, and excluding twins and retinoblastoma, that child’s siblings have approximately double the risk of the general population for developing childhood cancer. However, this excess could well be entirely accounted for by familial syndromes. In up to 25% of cases where a child who is a monozygotic twin has leukaemia, their cotwin will also develop leukaemia. These cases are usually due to in utero transfer of leukaemic or pre- leukaemic cells rather than being genetically determined. There is no evidence either of a raised risk of cancer or genetic disease among the offspring of survivors who do not themselves have a hereditary cancer syndrome or that the parents of children with cancer have an increased risk of cancer in the absence of known hereditary syndromes. A rapidly growing body of research has found significantly raised or reduced risk of ALL, neuroblastoma, and other childhood cancers associated with polymorphic variants of certain genes, sometimes interacting with exogenous factors, though many of these findings remain to be replicated.