Etiology. Childhood malignancy is a relatively rare event (it represents only about 2% of all cancer cases), affecting 1 child in 500 by 15 years of age

Incidence

Childhood malignancy is a relatively rare event (it represents only about 2% of all cancer cases), affecting 1 child in 500 by 15 years of age, and 1 in 300 to 330 by age 19.

Nevertheless, after trauma, it is the second most common cause of death in children older than 1 year.

Each year, approximately 130 new cases of cancer are identified per million children younger than 15 years (or about 1 in 7000). Leukemia is the most common form of cancer in children, and brain tumors are the most common solid tumor of childhood (Table 9.1). Lymphomas are the next most common malignancy in children, followed by neuroblastoma, soft tissue sarcomas, Wilms' tumor, germ cell tumors, osteosarcoma, and retinoblastoma.

Table 9.1

Frequency of Cancer Diagnoses in Childhood (by Arnold G. Coran, 2012)
Type of Cancer	Percentage of Total
Leukemia
Brain tumors
Lymphoma
Neuroblastoma
Sarcoma
Wilms' tumor
Osteosarcoma
Retinoblastoma
Liver tumors

A slightly different distribution is seen among 15- to 19-year-olds, in whom Hodgkin disease and germ cell tumors are the most frequently diagnosed malignancies; non-Hodgkin lymphoma, nonrhabdomyosarcoma soft tissue sarcoma, osteosarcoma, Ewing sarcoma, thyroid cancer, and melanoma also occur with an increased incidence.

In general, the incidence of childhood cancer is greatest during the first year of life, peaks again in children aged 2 to 3 years, and then slowly declines until age 9. The incidence then steadily increases again through adolescence. Each tumor type shows a different age distribution pattern, however. Variations by gender are also seen. For example, Hodgkin disease, ALL, brain tumors, neuroblastoma, hepatoblastoma, Ewing sarcoma, and rhabdomyosarcoma are more common in boys than in girls younger than 15 years, whereas only osteosarcoma and Ewing sarcoma are more common in boys than in girls older than 15 years. However, girls in the older age group have Hodgkin disease and thyroid cancer more frequently than boys do.

Distribution also varies by race: White children generally have a 30% greater incidence of cancer than do black children.

Despite intensive research over several decades, very little is known about the causes of most childhood cancers. Some of the most well-established risk factors are genetic in nature. An increasingly long list of hereditary syndromes, mostly associated with identified single gene defects, carry a raised risk of specific childhood cancers. Constitutional chromosomal abnormalities are implicated in about 1% of all childhood cancer.

What causes cancer?

Cancer results from a malignant transformation (carcinogenesis) of normal cells. A characteristic feature of cancer cells is their ability to proliferate uncontrollably, thus establishing themselves at other tissues to form secondary foci (metastasis). Additionally, cancer cells serve no useful purpose. Cancer cells metastasize via the circulation through the blood or lymphatics, by unintentional transplantation from one site to another during surgery, and by local extension.

Researchers have found that cancer develops from mutations within the genes of cells. Thus, cancer is a genetic disease. Cancer susceptibility genes are of two types. Some are oncogenes, which activate cell division and influence embryonic development, and some are tumor suppressor genes, which halt cell division.

These genes are typically found in normal human cells, but certain kinds of mutations may transform the normal cells. Inherited defects may cause a genetic mutation, whereas exposure to a carcinogen may cause an acquired mutation. Current evidence indicates that carcinogenesis results from a complex interaction of carcinogens and accumulated mutations in several genes.

¤ Some forms of cancer and precancerous lesions result from genetic predisposition either directly (as in Wilms' tumor and retinoblastoma) or indirectly (in association with inherited conditions such as Down syndrome or immunodeficiency diseases).

¤ High-frequency radiation, such as ultraviolet and ionizing radiation, damages the genetic material known as deoxyribonucleic acid (DNA), possibly inducing genetically transferable abnormalities. Other factors, such as a person's tissue type and hormonal status, interact to potentiate radiation's carcinogenic effect. Examples of substances that may damage DNA and induce carcinogenesis include: alkylating agents — leukemia; aromatic hydrocarbons and benzopyrene (from polluted air) — lung cancer; asbestos — mesothelioma of the lung; tobacco — cancer of the lung, oral cavity and upper airways, esophagus, pancreas, kidneys, and bladder; vinyl chloride — angiosarcoma of the liver.

Diet has also been implicated, especially in the development of GI cancer as a result of a high animal fat diet. Additives composed of nitrates and certain methods of food preparation — particularly charbroiling — are also recognized factors.

¤ In animal studies of the ability of viruses to transform cells, some human viruses exhibit carcinogenic potential. For example, the Epstein-Barr virus, the cause of infectious mononucleosis, has been linked to Burkitt's lymphoma and nasopharyngeal cancer.

¤ The role of hormones in carcinogenesis is still controversial, but it seems that excessive use of some hormones, especially estrogen, produces cancer in animals. Also, the synthetic estrogen diethylstilbestrol causes vaginal cancer in some daughters of women who were treated with it. It's unclear, however, whether changes in human hormonal balance retard or stimulate cancer development.

¤ Immune response. Other factors that interact to increase susceptibility to carcinogenesis are immunologic competence, age, nutritional status, hormonal balance, and response to stress. Theoretically, the body develops cancer cells continuously, but the immune system recognizes them as foreign cells and destroys them. This defense mechanism, known as immunosurveillance, has two major components: humoral immune response and cell-mediated immune response. Their interaction promotes antibody production, cellular immunity, and immunologic memory. Presumably, the intact human immune system is responsible for spontaneous regression of tumors.

Дата добавления: 2014-10-15