Gale Encyclopedia of Genetic Disorder / Gale Encyclopedia of Genetic Disorders, Two Volume Set - Volume 1 - A-L - I

Canavan-VanBogaert-Bertrand disease see

Canavan disease

I Cancer

Definition

Cancer is not just one disease, but a large group of diseases characterized by uncontrolled and abnormal growth of the cells in the human body and the ability of these cells to spread to distant sites (metastasis). If the spread is not controlled, cancer can result in death.

Description

Cancer, by definition, is a disease of the genes. Genes are formed from deoxyribonucleic acid (DNA) and located on chromosomes. They carry the hereditary instructions for the cell to make the proteins required for many body functions. Proteins are special chemical compounds that mostly contain carbon, hydrogen, oxygen, and nitrogen. They are required by our bodies to carry out all the processes that allow us to breathe, think, move, etc.

Throughout people’s lives, the cells in their bodies are growing, dividing, and replacing themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. A change (mutation) occurring in the DNA molecules can disrupt the genes and produce faulty proteins and cells. Abnormal cells can start dividing uncontrollably, eventually forming a new growth known as a “tumor” or “neoplasm” (medical term for cancer meaning “new growth”). In a healthy individual, the immune system can recognize the neoplastic cells and destroy them before they get a chance to divide. However, some abnormal cells may escape immune detection and survive to become cancerous.

Tumors are of two types, benign or malignant. A benign tumor is slow growing and does not spread or invade surrounding tissue. Once the tumor is removed, it usually will not start growing again. A malignant tumor, on the other hand, invades surrounding tissue and can spread to other parts of the body, often very distant from the location of the first tumor. Malignant tumors can be removed, but if the cancer cells have spread too much, the cancer becomes very difficult, if not impossible, to treat.

Most cancers are caused by changes in the cell’s DNA that result from exposure to a harmful environment. Environmental factors responsible for causing the initial

mutation in the DNA are called carcinogens. Other factors can cause cancer as well. For example, certain hormones have been shown to have an effect on the growth or control of a particular cell line. Hormones are substances made by one organ and passed through the bloodstream to affect the function of other cells in another organ.

While there is scientific evidence that both environmental and genetic factors play a role in most cancers, only 5-10% of all cancers are classified as hereditary. This means that a faulty gene which may cause cancer is passed from parent to child. This results in a greater risk for that type of cancer in the offspring of the family. However, if someone has a cancer-related gene, it does not mean they will automatically get cancer. Rather, this person is thought to be “predisposed” to a type of cancer, or more likely to get this cancer when compared to the general population. Various cancers are known to have a hereditary component in some cases. A few examples are breast cancer, colon cancer, ovarian cancer, skin cancer and prostate cancer.

Aside from genes, certain physiological traits that are inherited can contribute to cancers as well. For example, fair skin makes a person more likely to develop skin cancer, but only if they also have prolonged exposure to intensive sunlight.

There are several different types of cancers. Some of the most common types include:

•Carcinomas These cancers arise in the epithelium (the layers of cells covering the body’s surface and lining the internal organs and various glands). About 80% of human cancers fall into this category. Carcinomas can be subdivided into two subtypes: adenocarcinomas and squamous cell carcinomas. Adenocarcinomas are cancers that develop in an organ or a gland, while squamous cell carcinomas refer to cancers that originate in the skin.

•Melanomas This form also originates in the skin, usually in the pigment cells (melanocytes).

•Sarcomas These are cancers of the supporting tissues of the body, such as bone, muscle, cartilage, and fat.

•Leukemias Cancers of the blood or blood-forming organs.

•Lymphomas This type affects the lymphatic system, a network of vessels and nodes that acts as a filter in the body. It distributes nutrients to blood and tissue and prevents bacteria and other foreign substances from entering the bloodstream.

•Gliomas Cancers of the nerve tissue.

The most common cancers are skin cancer, lung cancer, colon and rectal (colorectal) cancer, breast cancer (in

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women), and prostate cancer (in men). In addition, cancer of the kidneys, ovaries, uterus, pancreas, bladder, and blood and lymph node cancer (leukemias and lymphomas) are also included among the 12 major cancers that affect most Americans.

Genetic profile

Three classes of genes are believed to play roles in the development of cancer. These are:

•Proto-oncogenes. These genes encourage and promote the normal growth and division of cells. When they are defective, they become oncogenes. Oncogenes are overactive proto-oncogenes and they cause excessive cell multiplication that can lead to tumors.

•Tumor suppressor genes. These act as brakes on cell growth. They prevent cells from multiplying uncontrollably. If these genes are defective, there is no control over cell growth and tumors can result.

•DNA repair genes. These genes ensure that each strand of DNA is correctly copied during cell division. When these genes do not function properly, the replicated DNA is likely to have mistakes. This causes defects in other genes and can also lead to tumor formation.

As stated above, approximately 5-10% of cancers have a hereditary component. In these cancers, a child does not inherit cancer from his parents. Rather, he inherits a predisposition to cancer. For example, he may inherit a faulty tumor suppressor gene. This gene is not able to control cell growth but the corresponding gene inherited from the other parent is still functional. Cell growth is then under control. However, as this child grows up, radiation, pollution, or any other harmful environmental factor could change the healthy gene, making it abnormal as well. When both of these tumor suppressor genes are not functioning, a tumor will most likely develop. Defects in proto-oncogenes and DNA repair genes can be inherited as well, leaving a person more vulnerable to cancer than the general population.

Additionally, some cancers seem to be familial. In these cancers, there is not a specific gene that is responsible for the clustering of cancer in a family. However, a particular type of cancer may be seen more often than expected. It is suggested that this is due to a combination of genetic and environmental factors.

Demographics

One out of every four Americans will die from cancer. It is the second leading cause of death in this country, surpassed only by heart disease. Over 1.2 million new cases of cancer are diagnosed every year. The National Cancer Institute estimates that approximately 8.4 million

Americans alive in 2001 have a history of cancer. Some of these people have been cured of their cancer while others are still affected with the disease and are undergoing treatment.

Anyone is at risk for developing cancer. Since the occurrence of cancer increases as a person ages, most of the cases are seen in adults who are middle-aged or older. Nearly 80% of cancers are diagnosed in people who are 55 years of age and older.

“Lifetime risk” is the term that cancer researchers use to refer to the probability that an individual will develop cancer over the course of their lifetime. In the United States, men have a one in two lifetime risk of developing cancer, and for women the risk is one in three. Overall, African-Americans are more likely to develop cancer than caucasians. They are also 33% more likely to die of cancer than caucasians.

The major risk factors for cancer are: tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment, and pollution.

Tobacco

Eighty to ninety percent of the lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of the mouth, pharynx, larynx, esophagus, pancreas, uterine cervix, kidney, and bladder. Smoking accounts for at least 30% of all cancer deaths. Recently, scientists have also shown that secondhand smoke (or passive smoking) can increase one’s risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in some cancers, such as liver cancer and breast cancer. Alcohol, in combination with tobacco, significantly increases the chances that an individual will develop mouth, pharynx, larynx, and esophageal cancers. The combined effect of tobacco and alcohol is greater than the sum of their individual effects.

Diet and physical activity

One-third of all cancer deaths are due to a poor adult diet. High-fat diets have been associated with cancers of the colon and rectum, prostate, endometrium, and possibly breast. Consumption of meat, especially red meat, has been associated with increased cancer at various sites, such as the colon and prostate. Additionally, a high calorie diet and low level of physical activity can lead to obesity. This increases the risk for cancer at various sites including the breast, colon and rectum, prostate, kidney, and endometrium.

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Sexual and reproductive behavior

The human papilloma virus, which is a sexually transmitted disease, has been shown to cause cancer of the cervix. Having many sexual partners and becoming sexually active early has been shown to increase a woman’s chances of contracting this disease and, therefore, developing cervical cancer. In addition, it has also been shown that women who do not bear any children or those who become pregnant late in life have an increased risk for both ovarian and breast cancer.

Hormone replacement therapy

As women go through menopause, a doctor may recommend hormone replacement therapy. This involves taking female hormones (called estrogen and progesterone) to control certain symptoms that occur during this time of a woman’s life, such as hot flashes and vaginal dryness. Taking estrogen alone can increase the risk for uterine cancer. However, progesterone is often prescribed at the same time to counteract the cancerous effects of estrogen. There is a questionable relationship between hormone replacement therapy and breast cancer as well. As of 2001, this relationship is not fully understood.

Family history

Some types of cancers tend to occur more frequently among members of a family. In most cases, this happens by chance or due to common family habits such as cigarette smoking or excessive sun exposure. However, this can also be due to a genetic predisposition that is passed from generation to generation. For example, if a certain gene called BRCA1 is defective in a given family, members of that family may have an increased risk to develop breast, colon, ovarian and prostate cancer. Other defective genes have been identified that can make a person susceptible to various types of cancer. Therefore, inheriting particular genes can increase a person’s chance to develop cancer.

Occupational hazards

There is strong evidence proving that occupational hazards account for 4% of all cancer deaths. For example, asbestos workers have an increased incidence of lung cancer. Similarly, bladder cancer is associated with dye, rubber, and gas workers; skin and lung cancer with smelters, gold miners and arsenic workers; leukemia with glue and varnish workers; liver cancer with PVC manufacturers; and lung, bone, and bone marrow cancer with radiologists and uranium miners.

Environment

High-frequency radiation has been shown to cause human cancer. Ultra-violet radiation from the sun

accounts for a majority of melanoma. Other sources of radiation are x rays, radioactive substances, and rays that enter the Earth’s atmosphere from outer space. Virtually any part of the body can be affected by these types of radiation, especially the bone marrow and the thyroid gland.

Additionally, being exposed to substances such as certain chemicals, metals, or pesticides can increase the risk of cancer. Asbestos is an example of a well-known carcinogen. It increases the risk for lung cancer. This risk is increased even further for a smoker who is exposed to asbestos over a period of time.

Signs and symptoms

Almost every tissue of the body can give rise to abnormal cells that cause cancer and each of these cancers is very different in symptoms and prognosis.

Cancer is also a progressive disease and goes through several stages. Each stage can produce a number of symptoms. Unfortunately, many types of cancer do not display any obvious symptoms or cause pain until the disease has progressed to an advanced stage. Early signs of cancer are often subtle and are easily mistaken for signs of other less-dangerous diseases.

Despite the fact that there are several hundred different types of cancers producing very different symptoms, the American Cancer Society has established the following seven symptoms as possible warning signs of cancer:

•Changes in the size, color, or shape of a wart or a mole

•A sore that does not heal

•Persistent cough, hoarseness, or sore throat

•A lump or thickening in the breast or elsewhere

•Unusual bleeding or discharge

•Chronic indigestion or difficulty in swallowing

•Any change in bowel or bladder habits

Many other diseases can produce similar symptoms. However, it is important to have these symptoms checked as soon as possible, especially if they do not stop. The earlier a cancer is diagnosed and treated, the better the chance of a cure. Many cancers, such as breast cancer, may not have any early symptoms. Therefore, it is important to undergo routine screening tests, such as breast self-exams and mammograms.

Diagnosis

If a person has symptoms of cancer, the doctor will begin with a complete medical history and a thorough physical examination. Different parts of the body will be examined to identify any variations from the normal size,

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KEY TERMS ( C O N T I N U E D )

Magnetic resonance imaging (MRI)—A technique that employs magnetic fields and radio waves to create detailed images of internal body structures and organs, including the brain.

Malignant—A tumor growth that spreads to another part of the body, usually cancerous.

Mammogram—A procedure in which both breasts are compressed/flattened and exposed to low doses of x rays, in an attempt to visualize the inner breast tissue.

Maori—A native New Zealand ethnic group.

Medulloblastoma—Tumor of the central nervous system derived from undifferentiated cells of the primitive medullary tube.

Melanoma—Tumor, usually of the skin.

Metachronous—Occurring at separate time intervals.

Metastasis—The spreading of cancer from the original site to other locations in the body.

Metastatic cancer—A cancer that has spread to an organ or tissue from a primary cancer located elsewhere in the body.

Multifocal breast cancer—Multiple primary cancers in the same breast.

Mutation—A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring.

Nitrates/nitrites—Chemical compounds found in certain foods and water that, when consumed, may increase the risk of gastric cancer.

Osteoma—A benign bone tumor.

Palliative—Treatment done for relief of symptoms rather than a cure.

Pancreas—An organ located in the abdomen that secretes pancreatic juices for digestion and hormones for maintaining blood sugar levels.

Pancreatitis—Inflammation of the pancreas.

Pelvic examination—Physical examination performed by a physician, often associated with a Pap smear. The physician inserts his/her finger into a woman’s vagina, attempting to feel the ovaries directly.

Pernicious anemia—A blood condition with decreased numbers of red blood cells related to poor vitamin B12 absorption.

Peutz-Jeghers syndrome (PJS)—Inherited syndrome causing polyps of the digestive tract and spots on the mouth as well as increased risk of cancer.

Polyp—A mass of tissue bulging out from the normal surface of a mucous membrane.

Primary cancer—The first or original cancer site, before any metastasis.

Prophylactic—Preventing disease.

(continued)

feel, and texture of the organ or tissue. Additionally, the doctor may order various other tests.

Laboratory tests on blood and urine are often used to obtain information about a person’s health. If cancer is suspected, a special test can be done that measures the amount of certain substances, called tumor markers, in the blood, urine, or particular tissues. These proteins are released from some types of cancer cells. Thus, the levels of these substances may be abnormal when certain cancers are present. However, laboratory tests alone cannot be used to make a definitive diagnosis of cancer. Blood tests are generally more useful in monitoring the effectiveness of the treatment or in following the course of the disease and detecting any signs of recurrence.

The doctor may also look for tumors by examining pictures of areas inside the body. The most common way to obtain these images is by using x rays. Other tech-

niques used to obtain pictures of the inside of the body include computed tomography scanning (CT scan), magnetic resonance imaging (MRI), and ultrasonography.

The most definitive diagnostic test is the biopsy. In this technique, a piece of tissue is surgically removed for examination under a microscope. A biopsy provides information about the cellular nature of the abnormality, the stage it has reached, the aggressiveness of the cancer, and the extent of its spread. Further analysis of the tissue obtained by biopsy defines the cause of the abnormality. Since a biopsy provides the most accurate analysis, it is considered the gold standard of diagnostic tests for cancer.

Regular screening examinations conducted by healthcare professionals can result in the early detection of various types of cancer. If detected at an early stage, treatment is more likely to be successful. For example, the American Cancer Society recommends an annual

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KEY TERMS ( C O N T I N U E D )

Prostatectomy—The surgical removal of the prostate gland.

Proximal—Near the point of origin.

Radiation—High energy rays used in cancer treatment to kill or shrink cancer cells.

Radiation therapy—Treatment using high-energy radiation from x-ray machines, cobalt, radium, or other sources.

Rectum—The end portion of the intestine that leads to the anus.

Semen—A whitish, opaque fluid released at ejaculation that contains sperm.

Seminal vesicles—The pouches above the prostate that store semen.

Sore—An open wound or a bruise or lesion on the skin.

Staging—A method of describing the degree and location of cancer.

Stomach—An organ that holds and begins digestion of food.

Synchronous—Occurring simultaneously.

Testicles—Two egg-shaped glands that produce sperm and sex hormones.

Testosterone—Hormone produced in the testicles that is involved in male secondary sex characteristics.

Trans-rectal ultrasound—A procedure where a probe is placed in the rectum. High-frequency sound waves that cannot be heard by humans are sent out from the probe and reflected by the prostate. These sound waves produce a pattern of echoes that are then used by the computer to create sonograms or pictures of areas inside the body.

Transvaginal ultrasound—A way to view the ovaries using sound waves. A probe is inserted into the vagina and the ovaries can be seen. Color doppler imaging measures the amount of blood flow, as tumors sometimes have high levels of blood flow.

Tumor—An abnormal growth of cells. Tumors may be benign (noncancerous) or malignant (cancerous).

Ultrasound—An imaging technique that uses sound waves to help visualize internal structures in the body.

Whipple procedure—Surgical removal of the pancreas and surrounding areas including a portion of the small intestine, the duodenum.

X ray—An image of the body made by the passing of radiation through the body.

X rays—High energy radiation used in high doses, either to diagnose or treat disease.

mammogram (x ray of the breast) for women over the age of 40 to screen for breast cancer. It also recommends a sigmoidoscopy (procedure using a thin, lighted tube to view the inside of the colon) every five years for people over the age of 50. This technique can check for colorectal cancer. Self-examinations for cancers of the breast, testes, mouth and skin can also help in detecting tumors.

Recent progress in molecular biology and cancer genetics have led to the development of several tests designed to assess one’s risk of developing certain types of cancer. This genetic testing involves looking closely at certain genes that have been linked to particular cancers. If these genes are abnormal, a person’s risk for certain types of cancer increases. At present, there are many limitations to genetic testing. The tests may be uninformative and they are useful to a very small number of people. Additionally, there are concerns about insurance coverage and employment discrimination for someone who has an increased risk for cancer. As of 2001, these tests are reserved only for very specific people. A hered-

itary cancer clinic can help to assess who may benefit from this type of testing.

Treatment

The aim of cancer treatment is to remove all or as much of the tumor as possible and to prevent the metastasis of the primary tumor. While devising a treatment plan for cancer, the likelihood of curing the cancer must be weighed against the side effects of the treatment. For example, if the cancer is very aggressive and a cure is not possible, then the treatment should be aimed at relieving the symptoms and controlling the cancer for as long as possible.

Cancer treatment can take many different forms and it is always tailored to the individual patient. The decision on which type of treatment to use depends on the type and location of cancer and the extent to which it has already spread. The doctor will also consider the patient’s age, sex, general health status, and personal

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TABLE 1

Childhood cancers associated with congenital syndromes or malformations

Syndrome or Anomaly	Tumour
Aniridia	Wilms tumor
Hemihypertrophy	Wilms tumor, hepatoblastoma, adrenocortical carcinoma
Genito-urinary abnormalities (including testicle maldescent)	Wilms tumor, Ewing sarcoma, nephroblastoma, testicular carcinoma
Beckwith-Wiedmann syndrome	Wilms tumor, neuroblastoma, adrenocortical carcinoma
Dysplastic naevus syndrome	Melanoma
Nevoid basal cell carcinoma syndrome	Basal cell carcinoma, medulloblastoma, rhabdomyosarcoma
Poland syndrome	Leukemia
Trisomy-21 (Down syndrome)	Leukemia, retinoblastoma
Bloom syndrome	Leukemia, gastrointestinal carcinoma
Severe combined immune deficiency disease	EBV-associated B-lymphocyte lymphoma/leukemia
Wiscott-Aldridge syndrome	EBV-associated B-lymphocyte lymphoma
Ataxia telangiectasia	EBV-associated B-lymphocyte lymphoma, gastric carcinoma
Retinoblastoma	Wilms tumor, osteosarcoma, Ewing sarcoma
Fanconi anemia	Leukemia, squamous cell carcinoma
Multiple endocrine neoplasia syndromes (MEN I, II, III)	Adenomas of islet cells, pituitary, parathyroids, and adrenal glands
	Submucosal neuromas of the tongue, lips, eyelids
	Pheochromocytomas, medullary carcinoma of the thyroid, malignant schwannoma, non-appendiceal
	carcinoid
Neurofibromatosis (von Recklinghausen syndrome)	Rhabdomyosarcoma, fibrosarcoma, pheochromocytomas, optic glioma, meningioma

treatment preferences. Treatment can be local, meaning that it seeks to destroy cancer cells in the tumor and the surrounding area. It can also be systemic, meaning that the treatment drugs will travel through the bloodstream and reach cancer cells all over the body. Surgery and radiation are local treatments. Chemotherapy, immunotherapy, and hormone therapy are examples of systemic treatments.

Surgery

Surgery can be used for many purposes in cancer therapy.

•Treatment surgery: This involves removal of the tumor to cure the disease. It is typically performed when the cancer is localized to a discrete area. Along with the cancer, some of the surrounding tissue may also be removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, lymph nodes that are near the tumor site may be examined and removed as well.

•Preventive surgery: Preventive or prophylactic surgery involves removal of an abnormal area that is likely to become malignant over time. For example, 40% of people with a colon disease, called ulcerative colitis, ultimately die of colon cancer. Rather than live with the fear of developing colon cancer, these people may choose to have their colons removed in order to reduce their risk of cancer.

•Diagnostic purposes: The most definitive tool for diagnosing cancer is a biopsy. Sometimes a biopsy can be

performed by inserting a needle through the skin. In other cases, the only way to obtain a tissue sample for biopsy is by performing a surgical operation.

•Cytoreductive surgery: This is a procedure in which the doctor removes as much of the cancer as possible. He then treats the remaining cancer cells with radiation therapy, chemotherapy, or both.

•Palliative surgery: This type of surgery is aimed at relieving cancer symptoms or slowing the progression of disease. It is not designed to cure the cancer. For example, if the tumor is very large or has spread to many places in the body, removing the entire tumor may not be an option. However, by decreasing the size of the tumor, pain may be alleviated. This is known as “debulking surgery.”

Radiation therapy

Radiation uses high-energy rays to kill cancer cells. This treatment may be used instead of surgery. It also may be used before surgery to shrink a tumor or after surgery to destroy any remaining cancer cells.

Radiation can be either external or internal. In the external form, the radiation comes from a machine that aims the rays at the tumor. In internal radiation (also known as brachytherapy), radioactive material is sealed in needles, seeds, or wires and placed directly in or near the tumor. Radiation may lead to various side effects, such as fatigue, hair loss, and a susceptibility to infections. However, these side effects can usually be controlled.

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A scanning electron micrograph (SEM) of cancer cells. (Photo Researchers, Inc.)

Chemotherapy

Immunotherapy

Chemotherapy is the use of drugs to kill cancer cells. The anticancer drugs are usually released into the entire body (systemic therapy) so as to destroy the hard-to- detect cancer cells that have spread and are circulating in the body. Chemotherapy is based on the principle that cancer cells are affected more dramatically than the normal cells because they are rapidly dividing. Chemotherapeutic drugs can be injected into a vein, the muscle, or the skin or they may be taken by mouth.

When chemotherapy is used before surgery, it is known as primary chemotherapy or “neoadjuvant chemotherapy.” Its purpose is usually to reduce the size of the tumor. The more common use of chemotherapy is in “adjuvant therapy.” In this form of treatment, chemotherapy is given after surgery to destroy any remaining cancer cells and to help prevent cancer from recurring. Chemotherapy can also be used in conjunction with radiation therapy.

The side effects of chemotherapy vary but can include susceptibility to infections, fatigue, poor appetite, weight loss, nausea, diarrhea, and hair loss. Decreased fertility can be a long-term side effect in some patients who undergo chemotherapy.

Immunotherapy, also called biological therapy, is the use of treatments that promote or support the body’s immune system response to cancer. The side effects of this immunotherapy are variable but include flu-like symptoms, weakness, loss of appetite, and skin rash. These symptoms will subside after the treatment is completed.

Bone marrow failure is a complication of chemotherapy. When high dose chemotherapy is used, this failure is anticipated. Bone marrow transplantation (BMT) or peripheral stem cell transplantation (PSCT) are techniques used to treat this complication. Both techniques provide healthy stem cells for the patient. Stem cells are immature cells that mature into blood cells. They can replace the patient’s own stem cells that have been damaged or destroyed by chemotherapy or radiation. It allows a patient to undergo very aggressive treatment for their cancer. Patients who receive BMT or PSCT have an increased risk of infection, bleeding, and other side effects due to the chemotherapy and radiation. Graft-ver- sus-host disease may also occur as well. This complication occurs when the donated marrow reacts against a patient’s tissues. It can occur any time after the trans-

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plant. Drugs may be given to reduce the risk of graft-ver- sus-host disease and to treat the problem if it occurs.

Hormone therapy

Hormone therapy is used to fight certain cancers that depend on hormones for their growth. Drugs can be used to block the production of hormones or change the way they work. Additionally, organs that produce hormones may be removed. As a result of this therapy, the growth of the tumor slows and survival may be extended for several months or years.

Alternative and complementary therapies

There are certain cancer therapies that have not been scientifically tested and approved. If these unproven treatments are used instead of the standard therapy, this is known as “alternative therapy.” If used along with standard therapy, this is known as “complementary therapy.” The use of alternative therapies must be carefully considered because some of these unproven treatments may have life-threatening side effects. Additionally, if someone uses alternative therapy, they may lose the opportunity to benefit from the standard, proven therapy. However, some complementary therapies may help to relieve symptoms of cancer, decrease the magnitude of side effects from treatment, or improve a patient’s sense of well-being. The American Cancer Society recommends that anyone considering alternative or complementary therapy consult a health care team.

Prevention

According to experts from leading universities in the United States, a person can reduce the chances of getting cancer by following these guidelines:

•Eating plenty of fruits and vegetables

•Exercising vigorously for at least 20 minutes every day

•Avoiding excessive weight gain

•Avoiding tobacco (including second hand smoke)

•Decreasing or avoiding consumption of animal fats and red meats

•Avoiding excessive amounts of alcohol

•Avoiding the midday sun (between 11 a.m. and 3 p.m.) when the sun’s rays are the strongest

•Avoiding risky sexual practices

•Avoiding known carcinogens in the environment or work place

Certain drugs that are currently being used for treatment can also be suitable for prevention. For example, the drug tamoxifen, also called Nolvadex, has been very

effective against breast cancer and is now thought to be helpful in the prevention of breast cancer. Similarly, retinoids derived from vitamin A are being tested for their ability to slow the progression or prevent head and neck cancers.

Prognosis

Most cancers are curable if detected and treated at their early stages. A cancer patient’s prognosis is affected by many factors, particularly the type of cancer the patient has, the stage of the cancer, the extent to which it has metastasized and the aggressiveness of the cancer. In addition, the patient’s age, general health status and the effectiveness of the treatment being pursued are also important factors.

To help predict the future outcome of cancer and the likelihood of recovery from the disease, five-year survival rates are used. The five-year survival rate for all cancers combined is 59%. This means that 59% of people with cancer are expected to be alive five years after they are diagnosed. These people may be free of cancer or they may be undergoing treatment. It is important to note that while this statistic can give some information about the average survival of cancer patients in a given population, it cannot be used to predict individual prognosis. No two patients are exactly alike. For example, the five-year survival rate does not account for differences in detection methods, types of treatments, additional illnesses, and behaviors.

Resources

BOOKS

American Cancer Society. Cancer Facts & Figures 2000.

American Cancer Society, 2000.

Buckman, Robert. What You Really Need to Know about

Cancer: A Comprehensive Guide for Patients and Their Families. Johns Hopkins University Press, 1997.

Murphy, Gerald P. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment and Recovery. American Cancer Society, 1997.

PERIODICALS

Ruccione, Kathy. “Cancer and Genetics: What We Need to Know.” Journal of Pediatric Oncology Nursing 16 (July 1999): 156-171.

“What You Need to Know about Cancer.” Scientific American 275, no. 3 (September 1996).

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd. NE, Atlanta, GA 30329. [phone]. http://www.cancer.org .

American Foundation for Urologic Disease, Inc. 1128 North Charles St., Baltimore, MD 21201-5559. [phone].http://www.afud.org .

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American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038. [phone] or [phone].http://www.liverfoundation.org .

National Cancer Institute. Office of Communications, 31 Center Dr. MSC 2580, Bldg. 1 Room 10A16, Bethesda, MD 20892-2580. [phone]. http://www.nci.nih

.gov .

National Familial Pancreas Tumor Registry. Johns Hopkins Hospital, Weinberg Building, Room 2242, 401 North Broadway, Baltimore, MD 21231-2410. [phone].http://www.path.jhu.edu/pancreas .

University of Texas M.D. Anderson Cancer Center. 1515 Holcombe Blvd., Houston, TX 77030. [phone].http://www.mdanderson.org .

WEBSITES

American Cancer Society. Cancer Resource Center.http://www3.cancer.org/cancerinfo/ .

National Cancer Institute. CancerNet.http://cancernet.nci.nih.gov .

University of Pennsylvania Cancer Center. Oncolink.http://cancer.med.upenn.edu .

Mary E. Freivogel, MS

I Cardiofaciocutaneous

syndrome

Definition

Cardiofaciocutaneous syndrome is an extremely rare genetic condition present at birth and characterized by mental retardation, slow growth, and abnormalities of the heart, face, skin, and hair. There is no cure for cardiofaciocutaneous syndrome. Treatment centers on the correction of heart abnormalities and strategies to improve the quality of life of the affected individual.

Description

Cardiofaciocutaneous syndrome was first identified and described in 1986 by J. F. Reynolds and colleagues at the Shodair Children’s Hospital in Helena, Montana and at the University of Utah. These physicians identified and described eight children with a characteristic set of mental and physical changes including abnormal skin conditions, an unusual face, sparse and curly hair, heart defects, and mental retardation. These physicians named the syndrome based on the changes of the heart (cardio), face (facio), and skin (cutaneous). Since that time, physicians have used the descriptions originally put forth by Dr. Reynolds to identify other children with cardiofaciocutaneous syndrome.

Scientific research conducted over the past decade suggests that cardiofaciocutaneous syndrome is associated with a change in the genetic material. However, it is still not known precisely how this change in the genetic material alters growth and development in the womb to cause cardiofaciocutaneous syndrome.

Cardiofaciocutaneous syndrome can sometimes be confused with another genetic syndrome, Noonan syndrome. Children with Noonan syndrome have abnormalities in the same genetic material as those with cardiofaciocutaneous syndrome, and the two syndromes share some similar physical characteristics. Many scientists believe that the two diseases are different entities and should be regarded as separate conditions, while others believe that Noonan syndrome and cardiofaciocutaneous syndrome may be variations of the same disease.

Genetic profile

Recent research has shown that people with cardiofaciocutaneous syndrome have changes in a gene located on a region of human chromosome 12 (locus 12q24), but the precise gene and genetic alteration is unknown.

In almost all cases of cardiofaciocutaneous syndrome, there is no family history of the disease. These cases are thought to represent new genetic changes that occur randomly and with no apparent cause and are termed sporadic. While the cause of the genetic change is still unclear, some studies suggest that the age of the father might be important in the genesis of the disease. In 20 cases for which information was available, scientists noted that fathers of affected children tended to be older (average age of 39 years) when the child was conceived. Therefore, it is believed that a change in the genetic material of the father’s sperm may occur as the man ages, and that he may, in turn, pass this genetic change to the child, resulting in cardiofaciocutaneous syndrome.

Only one abnormal gene in a gene pair is necessary to display the disease. This is an example of a dominant gene (i.e. the abnormal gene of the gene pair dominates over the normal gene, resulting in the syndrome).

Demographics

Cardiofaciocutaneous syndrome is an extremely rare condition. Because the syndrome is relatively new and only a small number of physicians have actual first-hand experience with the diagnosis of the syndrome, some children with the syndrome may not be diagnosed, particularly if they are living in areas where sophisticated medical care is not available. As a result, it is difficult to know how many children are affected by cardiofaciocu-

syndrome Cardiofaciocutaneous

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Cardiofaciocutaneous syndrome

K E Y T E R M S

Autosomal dominant—A pattern of genetic inheritance where only one abnormal gene is needed to display the trait or disease.

Bitemporal constriction—Abnormal narrowing of both sides of the forehead.

Macrocephaly—A head that is larger than normal.

Noonan syndrome—A genetic syndrome that possesses some characteristics similar to cardiofaciocutanous syndrome. It is unclear whether the two syndromes are different or two manifestations of the same disorder.

Sporadic—Isolated or appearing occasionally with no apparent pattern.

taneous syndrome. However, scientists estimate that less than 200 children worldwide are presently affected by this condition.

Because the syndrome is so rare, it is not known whether the disease is distributed equally among different geographic areas or whether different ethnic groups have higher incidences of the syndrome.

Signs and symptoms

Individuals with cardiofaciocutaneous syndrome have distinct malformations of the head and face. An unusually large head (macrocephaly), a prominent forehead, and abnormal narrowing of both sides of the forehead (bitemporal constriction) are typical. A short, upturned nose with a low nasal bridge and prominent external ears that are abnormally rotated toward the back of the head are also seen. In most cases, affected individuals have downward slanting eyelid folds, widely spaced eyes, drooping of the upper eyelids, inward deviation of the eyes, and other eye abnormalities. In addition to having unusually dry, brittle, curly scalp hair, affected individuals may lack eyebrows and eyelashes.

Individuals with cardiofaciocutaneous syndrome may also have a range of skin abnormalities, varying from areas of skin inflammation to unusually dry, thickened, scaly skin over the entire body. Most affected individuals also have congenital heart defects, particularly obstruction of the normal flow of blood from the right chamber of the heart to the lungs and/or an abnormal opening in the wall that separates two of the heart chambers.

In addition, most individuals with the disorder experience growth delays, mild to severe mental retardation,

and abnormal delays in the acquisition of skills requiring the coordination of muscular and mental activity. Other abnormalities encountered in children with cardiofaciocutaneous syndrome include seizures, abnormal movements of the eye, poor muscle tone, and poor digestion. In some cases, additional abnormalities may be present.

Diagnosis

The diagnosis of cardiofaciocutaneous syndrome relies on physical exam by a physician familiar with the condition and by radiographic evaluation, such as the use of x rays or ultrasound to define abnormal or missing structures that are consistent with the criteria for the condition (as described above). Although a diagnosis may be made as a newborn, most often the features do not become fully evident until early childhood.

There is no laboratory blood test or commercially available genetic test that can be used to identify people with cardiofaciocutaneous syndrome. However, because the condition is so rare, advanced genetic analysis may be available as part of a research study to determine if changes in regions of chromosome 12 are present.

Cardiofaciocutaneous syndrome can be differentiated from Noonan syndrome by the presence of nervous system abnormalities, such as low muscle tone, seizures, and abnormal movements of the eye, as well as by typical changes in the hair and skin.

Treatment and management

There is no cure for cardiofaciocutaneous syndrome. The genetic change responsible for cardiofaciocutaneous syndrome is present in every cell of the body and, at the current time, there is no means of correcting this genetic abnormality.

Treatment of the syndrome is variable and centers on correcting the different manifestations of the condition. For children with heart defects, surgical repair is often necessary. This may take place shortly after birth if the heart abnormality is life threatening, but often physicians will prefer to attempt a repair once the child has grown older and the heart is more mature. For children who experience seizures, lifelong treatment with anti-seizure medications is often necessary. Oral or topical medications may also be used to treat the inflammatory skin conditions and provide some symptomatic and cosmetic relief.

During early development and progressing into young adulthood, children with cardiofaciocutaneous should be educated and trained in behavioral and mechanical methods to adapt to their disabilities. This program is usually initiated and overseen by a team of

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