Incidence and Types of Cancer

In 2012, approximately 12,060 children (from birth to 14 years of age) in the United States will be diagnosed with cancer, and approximately 1340 will die from the disease, one third of these from leukemia.¹

The types of malignancies in children are vastly different from those that affect adults. The most common types of cancer among adults include prostate, breast, lung, and colon. Children (birth to 14 years of age) with leukemias and brain tumors account for 61% of childhood cancers; neuroblastoma and soft tissue or bone sarcomas are less common. Although many adult cancers have associated lifestyle factors that could theoretically be avoided, such as smoking and lifetime exposure to sun, very few environmental factors have been linked to pediatric malignancies. Yet more data are emerging that the developing child may be affected by parental exposures before conception, exposures in utero, and the contents of breast milk.2,3

The incidence of cancer among adolescents and young adults represents only 2% of all invasive cancers. However, the malignancy rate in this age group (15- to 39-year-olds) is three times higher than that in children younger than 15 years. Each year about 70,000 adolescents and young adults will be diagnosed with cancer. The following are the most common cancers diagnosed among the 15- to 39-year-old population in the United States³ (these cancers are discussed in the appropriate chapters):

Most childhood cancers originate from the mesodermal germ layer that gives rise to connective tissue, bone, cartilage, muscle, blood, blood vessels, gonads, kidney, and the lymphatic system. Thus the more common childhood cancers are leukemias, sarcomas, and embryonic tumors. Embryonic tumors originate during intrauterine life. These tumors contain abnormal cells that appear to be immature embryonic tissue, unable to mature or differentiate into fully developed functional cells. Embryonic tumors are diagnosed early in life (usually before 5 years of age). Embryonic tumors often contain the term blast cell in their name, which refers to the immature nature of the cells.

Leukemia is the most common malignancy in children and the most common type of leukemia is acute lymphoblastic leukemia (ALL), which represents approximately 75% of all pediatric leukemia cases. Although the presenting signs of the various types of leukemia may be similar, the treatment and response to treatment of childhood leukemias vary greatly (see Chapter 30).

CNS tumors are the most common types of solid tumors in children and account for 27% of all childhood cancers¹ (see Chapter 20). Not all brain tumors are diagnosed malignant by histologic studies, but even a benign tumor can have devastating effects, depending on the anatomic location. The treatment for brain tumors in children often presents difficulties because therapies, such as radiation, may have debilitating effects on the developing brain, particularly in children younger than 3 years of age.

Lymphoma, including non-Hodgkin lymphoma and Hodgkin lymphoma, is a malignancy that occurs in children and adults. However, the subtypes of lymphoma and treatments in the two populations often differ (see Chapter 30).

Many pediatric solid tumors usually develop only in children but in very rare instances may occur in adults. These tumors include neuroblastoma, Wilms tumor, rhabdomyosarcoma, retinoblastoma, osteosarcoma, and Ewing sarcoma.

Childhood cancers are most often diagnosed during peak times of physical growth. In general, they are extremely fast growing, with 80% having distant spread (metastases) at diagnosis. Overall, cancer is 10% to 25% more common in white than in black children. Boys are more likely to develop cancer than girls.

Etiology

The causes of cancer in children are largely unknown. A few environmental factors are known to predispose a child to cancer, but causal factors have not been established for most childhood cancers. A number of host factors, many of which are genetic risk factors or congenital conditions, have been implicated in the development of childhood cancer (Table 14-1). It is most likely the interaction of many factors that produces cancer, a concept referred to as multiple causation or multifactorial etiology. According to this premise, cancer develops because of the predisposing characteristics of the person and the interaction with environmental causes.

The multiple causation concept is useful when the results of epidemiologic studies are interpreted. For example, laboratory and epidemiologic studies may indicate that exposure to a certain chemical can cause leukemia, but not all children exposed to that chemical will develop leukemia. Additional studies will be needed to determine what other factors must interact with chemical exposure to cause the disease.

Genetic Factors

Oncogenes and tumor-suppressor genes are associated with the development of childhood cancer (Table 14-2; also see Chapter 12). Proto-oncogenes code for proteins that help to regulate normal cell growth and differentiation. If mutated, proto-oncogenes become oncogenes that help to turn normal cells into cancer cells. Changes produced by specific oncogenes cause the cell cycle to become dysregulated. An example of an oncogene identified in pediatric cancer is N–myc, which is involved in neuroblastoma and glioblastoma. Tumor-suppressor genes arise from genes that normally suppress cancer cell proliferation but have lost their suppressor function, thus leading to uncontrolled growth. Some childhood cancers identified with tumor-suppressor genes include osteosarcoma, leukemia, rhabdomyosarcoma, retinoblastoma, and Wilms tumor.⁴

TABLE 14-2

SELECTED ONCOGENES AND TUMOR-SUPPRESSOR GENES ASSOCIATED WITH CHILDHOOD CANCER

GENE	ASSOCIATED PEDIATRIC TUMOR
Oncogenes
bcr-abl	Acute lymphoblastic leukemia
N-myc	Neuroblastoma
c-myb	Neural tumors, leukemia, lymphoma, rhabdomyosarcoma, Wilms tumor, neuroblastoma
erb B	Glioblastomas
N-ras	Neuroblastoma, leukemia
H/K-ras	Neuroblastoma, rhabdomyosarcoma, leukemia
ATM	Lymphoma, leukemia
Tumor-Suppressor Genes
Rb1	Retinoblastoma, sarcoma
WT1, WT2	Wilms tumor, leukemia
WTC	Wilms tumor
NF-1	Sarcoma, primitive neuroectodermal tumor, juvenile chronic myelocytic leukemia
NF-2	Brain tumors, melanoma, meningiomas
p16	Brain tumors, leukemia
TP53	Sarcoma, leukemia, brain tumors, lymphoma
DCC	Ewing sarcoma, rhabdomyosarcoma
p16INK4a	Glioma, leukemia
p15ARF	Glioblastoma, T-cell ALL
CDC2L1	Non-Hodgkin lymphoma, neuroblastoma

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