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Childhood Cancer

What is cancer?

Cancer is an abnormal growth of cells. Cancer cells rapidly reproduce despite restriction of space, nutrients shared by other cells, or signals sent from the body to stop reproduction. Cancer cells are often shaped differently than healthy cells, they do not function properly, and they can spread to many areas of the body. Oncology is the study of cancer and tumors.

The number of cells in each body tissue is tightly controlled. The number of new cells made equals the number needed to replace dying cells plus the number needed for growth and development. Unlike normal cells, tumors are clusters of cells that are capable of growing and dividing uncontrollably. Their growth is not regulated. Tumors can be benign (non-cancerous), or malignant (cancerous). Benign tumors tend to grow slowly and do not spread. Malignant tumors grow rapidly, can invade and destroy nearby normal tissues, and can spread throughout the body. The term "cancer" is used when a tumor is malignant. Cancer is malignant because it can be "locally invasive" and "metastatic":

• locally invasive - the tumor can invade the tissues surrounding it by sending out 'fingers' of cancerous cells into the normal tissue.
• metastatic - the tumor can send cells into other tissues in the body, which may be distant from the original tumor.

The original tumor is called the "primary tumor." Cells from this tumor can travel through the body and begin the formation of new tumors in other organs. These tumors are referred to as "secondary tumors." Cancerous cells travel through the blood (circulatory system) or lymphatic system to form secondary tumors. The lymphatic system is a series of small vessels that collect waste from cells, carrying it into larger vessels, and finally into lymph nodes. Lymph fluid eventually drains into the bloodstream.

When cancer spreads, it is still named after the part of the body where it started. For example, if kidney cancer spreads to the lungs, it is still kidney cancer, not lung cancer. (The lung cancer would be an example of a secondary tumor). "Staging" is the process of finding out whether cancer has spread and if so, how far. There is more than one system used for staging. Cancer is not just one disease but rather a group of diseases. All forms of cancer cause cells in the body to change and grow out of control.

What causes cancer?

There is no one single cause for cancer. Scientists believe that it is the interaction of many factors that produces cancer. The factors involved may be genetic, environmental, or constitutional characteristics of the individual.

Diagnosis, treatment, and prognosis for childhood cancers are different than for adult cancers. The main differences are the survival rate and the cause of the cancer. The overall survival rate for childhood cancer is about 72 percent, while in adult cancers the survival rate is 60 percent. This difference is thought to be because childhood cancer is more responsive to therapy, a child can tolerate more aggressive therapy, and the prognosis is better.

Childhood cancers often occur or begin in the stem cells, which are simple cells capable of producing other types of specialized cells that the body needs. A sporadic (occurs by chance) cell change or mutation is usually what causes childhood cancer. In adults, the type of cell that becomes cancerous is usually an "epithelial" cell, which are cells that line the body cavity and cover the body surface. Cancer occurs from environmental exposures to these cells over time. Adult cancers are sometimes referred to as "acquired" for this reason.

What are the risk factors for cancer?

As mentioned, some cancers, particularly in adults, have been associated with repetitive exposures or risk factors. A risk factor is anything that may increase a person's chance of developing a disease. A risk factor does not necessarily cause the disease, but it may make the body less resistant to it. The following risk factors and mechanisms have been proposed as contributing to cancer:

• Lifestyle factors such as smoking, high-fat diet, and working with toxic chemicals may be risk factors for some adult cancers. Most children with cancer, however, are too young to have been exposed to these lifestyle factors for any extended time.
• Family history, inheritance, and genetics may play an important role in some childhood cancers. It is possible for cancer of varying forms to be present more than once in a family. It is unknown in these circumstances if the disease is caused by a genetic mutation, exposure to chemicals near a family's residence, a combination of these factors, or simply coincidence.
• Some genetic disorders (i.e., Wiskott-Aldrich and Beckwith-Wiedemann syndrome) are known to alter the immune system. The immune system is a complex system that functions to protect our bodies from infection and disease. The bone marrow produces cells that later mature and function as part of the immune system. One theory suggests that the cells in the bone marrow, the stem cells, become damaged or defective, so when they reproduce to make more cells, they make abnormal cells or cancer cells. The cause of the defect in the stem cells could be related to an inherited genetic defect or exposure to a virus or toxin.
• Exposures to certain viruses such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV; the virus which causes acquired immune deficiency, or AIDS), have been linked to an increased risk of developing certain childhood cancers such as Hodgkin and non-Hodgkin lymphoma. Possibly, the virus alters a cell in some way. That cell then reproduces an altered cell and, eventually, these alterations become a cancer cell that reproduces more cancer cells.
• Environmental exposures such as pesticides, fertilizers, and power lines have been researched for a direct link to childhood cancers. There has been evidence of cancer occurring among non-related children in certain neighborhoods and/or cities. Whether prenatal or infant exposure to these agents causes cancer, or whether it is a coincidence, is unknown.
• Some forms of high-dose chemotherapy and radiation have been linked to cancer. In some cases, children that have been exposed to these agents may develop a second malignancy later in life. These strong anti-cancer agents can alter cells and/or the immune system. A second malignancy is a cancer that appears as a result from treatment of a different cancer.

How do genes affect cancer growth?

The discovery of certain types of genes that contribute to cancer has been an extremely important development for cancer research. Over 90 percent of cancers are observed to have some type of genetic alteration. Some of these alterations are inherited, while others are sporadic, which means they occur by chance or occur from environmental exposures (usually over many years). There are three main types of genes that can affect cell growth, and are altered (mutated) in certain types of cancers, including the following:

• oncogenes - these genes regulate the normal growth of cells. Scientists commonly describe oncogenes as similar to a cancer "switch" that most people have in their bodies. What "flips the switch" to make these oncogenes suddenly become unable to control the normal growth of cells and allowing abnormal cancer cells to begin to grow, is unknown.
• tumor suppressor genes - these genes are able to recognize abnormal growth and reproduction of damaged cells, or cancer cells, and can interrupt their reproduction until the defect is corrected. If the tumor suppressor genes are mutated, however, and they do not function properly, tumor growth may occur.
• mismatch-repair genes - these genes help recognize errors when DNA is copied to make a new cell. If the DNA does not "match" perfectly, these genes repair the mismatch and correct the error. If these genes are not working properly, however, errors in DNA can be transmitted to new cells, causing them to be damaged. Usually the number of cells in any of our body tissues is tightly controlled so that new cells are made for normal growth and development, as well as to replace dying cells. Ultimately, cancer is a loss of this balance due to genetic alterations that "tip the balance" in favor of excessive cell growth.

What are the difference types of childhood cancer?

Childhood cancers vary widely in effects, diagnosis and treatment. For more information about specific cancers, choose one below.

Hematologic malignancies

• Acute lymphoid leukemia (ALL)
• Acute myelogenous leukemia (AML)
• Chronic myelogenous leukemia (CML)
• Juvenile myelomonocytic leukemia (JMML)
• Myelodysplastic syndrome (MDS)
• non-Hodgkin lymphoma (NHL)
  • Burkitt's lymphoma
  • cutaneous or skin lymphoma
  • Epstein Barr virus-related lymphoma
  • large cell lymphoma
  • lymphoblastic lymphoma
  • lymphoproliferative disorders

• Hodgkin Disease
  • Hodgkin in immunocompromised hosts
  • lymphocyte depleted
  • lymphocyte predominant
  • mixed cellularity
  • nodular sclerosing

Solid tumors

• Brain tumors
• Desmoid tumor
• Ewing's sarcoma (ES)
• Germ cell tumors
• Hepatoblastoma
• Hepatocellular carcinoma
• Nasopharyngeal carcinoma
• Neuroblastoma (NBL) and ganglioneuroblastoma
• Osteosarcoma
• Retinoblastoma (RB)
• Rhabdomyosarcoma (RMS)
• Soft tissue sarcomas
• Thyroid carcinoma
• Wilm's tumor (WT)

Related diseases

Primary marrow dysfunction

• Aplastic anemia (AA)
• Diamond-Blackfan anemia (DBA)
• Kostmann's syndrome (KS)
• Sickle cell anemia (SSA)
• Thalassemia (THAL)

Immunodeficiency

• Familial erthyrophagocytic lymphohistiocytosis (FEL)
• Severe combined immunodeficiency syndromes (SCID)
• Wiskott-Aldrich syndrome (WAS)

Storage or metabolic diseases

• Adrenal leukodystrophy (ALD)
• Gaucher's disease
• Hurler's syndrome
• Mucopolysaccharidoses (MPS)

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