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development. Because of this characteristic, these tumors are frequently designated with the suffix “ -blastoma ” (e.g., nephroblastoma [Wilms tumor], retinoblastoma, neuroblastoma). 2 Wilms tumor (discussed in Chapter 25) and neuroblastoma are particularly illustrative of this type of childhood tumor. Biology of Childhood Cancers As with adult cancers, there probably is no one cause of childhood cancer. Although a number of genetic conditions are associated with childhood cancer, such conditions are relatively rare, suggesting an interac- tion between genetic susceptibility and environmental exposures. The most notable heritable conditions that impart susceptibility to childhood cancer include Down syndrome (20- to 30-fold increased risk of acute lym- phoblastic leukemia), 1 neurofibromatosis (NF) type 1 (neurofibromas, optic gliomas, brain tumors), NF type 2 (acoustic neuroma, meningiomas), xeroderma pigmen- tosum (skin cancer), ataxia-telangiectasia (lymphoma, leukemia), and the Beckman-Wiedemann syndrome (Wilms tumor). 2,69 While constituting only a small percentage of childhood cancers, the biology of a number of these tumors illustrates several important biologic aspects of neoplasms, such as the two-hit theory of recessive tumor-suppressor genes (e.g., RB gene mutation in retinoblastoma); defects in DNA repair; and the histo- logic similarities between embryonic organogenesis and oncogenesis. Syndromes associated with defects in DNA repair include xeroderma pigmentosa, in which there is increased risk of skin cancers due to defects in repair of DNA damaged by ultraviolet light. The development of childhood cancers has also been linked to genetic imprinting, which is characterized by selective inacti- vation of one of the two alleles of a certain gene (dis- cussed in Chapter 5). 69 The inactivation is determined by whether the gene is inherited from the mother or father. For example, normally the maternal allele for the insulin-like growth factor-2 (IGF-2) gene is inactivated (imprinted). The Beckwith-Wiedemann syndrome is an overgrowth syndrome characterized by organomegaly, macroglossia (enlargement of the tongue), hemihyper- trophy (muscular or osseous hypertrophy of one side of the body or face), renal abnormalities, and enlarged adrenal cells. 2 The syndrome, which reflects changes in the imprinting of IGF-2 genes located on chromo- some 11, is also associated with increased risk of Wilms tumor, hepatoblastoma, rhabdomyosarcoma, and adre- nal cortical carcinoma. Diagnosis andTreatment Because many childhood cancers are curable, early detection is imperative. In addition, there are several types of cancers for which less therapy is indicated than for more advanced disease. Therefore, early detection often minimizes the amount and duration of treatment required for cure.

 Childhood Cancers and Late Effects on Cancer Survivors Despite progressively improved 5-year survival rates, from 56% in 1974 to 75% in 2000, cancer remains the leading cause of disease-related deaths among children between 1 to 14 years in the United States. 68 Leukemia (discussed in Chapter 11) accounts for one-third of cases of cancer in children ages 1 to 14 years. 1 Cancer of the brain and other parts of the nervous system are the second most common, followed by tissue sarcoma, neuroblastoma, renal cancer (Wilms tumor, discussed in Chapter 26), and non-Hodgkin and Hodgkin lym- phoma (discussed in Chapter 11). 1

Two young girls with acute lymphocytic leukemia are receiving chemotherapy (From National Cancer Institute Visuals. No. AV-8503-3437.)

Incidence andTypes of Childhood Cancers

The spectrum of cancers that affect children differs markedly from those that affect adults. Although most adult cancers are of epithelial cell origin (e.g., lung can- cer, breast cancer, colorectal cancers), childhood cancers usually involve the hematopoietic system (leukemia), brain and other parts of the nervous system, soft tissues, kidneys (Wilms tumor), and bone. 1,68 The incidence of childhood cancers is greatest during the first years of life, decreases during middle childhood, and then increases during puberty and adolescence. 68 During the first 2 years of life, embryonal tumors such as neuroblastoma, retinoblastoma, and Wilms tumor are among the most common types of tumors. Acute lymphocytic leukemia has a peak incidence in children 2 to 5 years of age. As children age, especially after they pass puberty, bone malignancies, lymphoma, gonadal germ cell tumors (testicular and ovarian carcinomas), and various carcinomas such as thyroid cancer and malignant melanoma increase in incidence. A number of the tumors of infancy and early child- hood are embryonal in origin, meaning that they exhibit features of organogenesis similar to that of embryonic