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Definition

Cancer is characterized by uncontrolled growth of cells in the body and the ability of these malignant cells to spread (metastasize) to distant sites within the body. If the spread is not controlled, cancer can result in death. Cancer is not just one disease but a group of almost one hundred different types of malignant diseases.

Description

Cancer, by definition, is a disease of the genes. A gene is a small part of DNA, which is the instruction manual of the cell. Genes hold the instructions to make proteins, which carry out many of the body's functions. It is these proteins that allow the human body to carry out all the processes that permit people to breathe, think, move, etc.

Throughout people's lives the cells in their bodies grow, divide, and replace themselves. Many genes produce proteins that are involved in controlling the processes of cell growth and division. An alteration (mutation) to the DNA molecule can disrupt some of the genes on the DNA molecule and produce faulty proteins. This causes a cell to loose restraint on growth. The abnormal cell begins to divide uncontrollably and eventually forms a new growth known as a tumor or neoplasm (medical terms for cancer meaning new growth). In a healthy body the immune system can recognize neoplastic (abnormal) cells and destroy them before they get a chance to divide. Even so, some mutant cells may escape immune detection and survive to develop into cancerous growths.

Tumors are divided into two general categories: benign or malignant. A benign tumor is slow growing and does not spread or invade surrounding tissue. Once it is removed it doesn't usually recur. A malignant tumor, on the other hand, invades surrounding tissue and can spread to other parts of the body. Malignant tumors can be removed; however, if the cancer cells have spread to the surrounding tissues, the tumor is likely to recur.

A majority of cancers are caused by changes in the cell's DNA that are due to the environment. Environ- mental factors that are responsible for causing the initial mutation in the DNA are called carcinogens. Internal factors can cause cancer as well. Certain hormones have been shown to have an effect the growth or control of a particular cell line. Hormones are substances made by one organ and passed through the bloodstream to perform a function in another organ.

While there is scientific evidence that both environ- mental and genetic factors play a role in most cancers, approximately 5–10% of all cancers are classified as hereditary (genetic). This means a faulty gene that leads to a cancer is passed from parent to child. This poses a greater risk for that particular type of cancer in certain descendants of the family. However, having a cancer- causing gene does not necessarily mean that person will automatically get cancer. Rather, it means that person is predisposed to a type of cancer, or more likely to get this cancer when compared to the general population. Cancers known to have a hereditary tendency in some cases include breast cancer, colon cancer, ovarian cancer, skin cancer, and prostate cancer.

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

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

• Carcinomas. These cancers arise in the epithelium (layers of cells in the skin 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, which are cancers that develop in an organ or a gland; and squamous cell carcinomas, cancers that originate in the skin.
• Melanomas. This form also originates in the skin, usually in the pigment cells (melanocytes), and can quick- ly metastasize to internal organs.
• Sarcomas. 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. Cancer of the lymphatic system, the network of vessels and nodes that acts as a filtration system, distributing nutrients to blood and tissue and preventing bacteria and other foreign substances from entering the bloodstream.
• Gliomas. Cancers of nerve tissue.

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

Almost every tissue can give rise to cells that cause cancer and each of these cancers is very different in its symptoms and prognosis. However, there are basic and similar genetic processes that lead to tumor growth in the human body. Genes are responsible for producing proteins that regulate cell growth and division. When these genes do not function properly, the proteins are abnormal and cells can grow uncontrollably. This results in the formation of a tumor. As more genetic mutations (changes) occur in this tumor, it becomes more life-threatening and has a greater chance of spreading to other parts of the body.

Three classes of genes appear to play a role in the development of cancer:

• Proto-oncogenes encourage and promote the normal growth and division of cells. When they are defective, they become oncogenes. Oncogenes are overactive proto-oncogenes that cause excessive cell multiplication that can lead to tumors.
• Tumor suppressor genes 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 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 errors. This causes defects in other genes and can lead to tumor formation in some cases.

Approximately 5–10% of cancers have a hereditary component. In these cancers a child does not inherit caner

from the parents. Rather, a predisposition to cancer is inherited. For example, a faulty tumor suppressor gene may be inherited. This gene is not able to control cell growth but the corresponding gene inherited from the other parent is still functional. Cell growth is under control. However, as a child grows up, radiation, pollution, or any other environmental factor could change the functional gene, making it defective as well. Now, neither of these tumor suppressor genes are functioning, and it is likely that a tumor will 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.

Some cancers seem to run in families. In these cancers there is no specific gene responsible for the clustering of cancer in a family. However, a particular type of cancer may be seen more often than in the general population. It is suggested that this is due to a combination of genetic and environmental factors.

Cancer kills one out of every four Americans. As of 2001 it was the second leading cause of death in the United States, surpassed only by heart disease. More than 1.2 million new cases of cancer are diagnosed every year in the United States. The National Cancer Institute estimates that approximately 8.4 million Americans alive in 2001 had a history of cancer. Some of these people were cured while others were still affected with the dis- ease and possibly undergoing treatment.

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

Lifetime risk is the term used to refer to the probability that an individual will develop cancer over the course of his or her lifetime. In the United States men have a one-in-two lifetime risk of developing cancer. For women, the risk is one in three. Overall, African Americans are more likely to develop cancer than Caucasians and are 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 lung cancer cases occur in smokers. Smoking has also been shown to be a contributory factor in cancers of mouth, pharynx, larynx, esophagus, pancreas, uterine cervix, kidney, and bladder. Smoking accounts for at least 30% of all cancer deaths. Scientists have shown that inhaling secondhand smoke (passive smoking) can increase one's risk of developing cancer.

Alcohol

Excessive consumption of alcohol is a risk factor in certain cancers such as liver 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. This is called synergy.

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, which increases the risk for cancer at various sites including the breast, colon and rectum, prostate, kidney, and endometrium.

Sexual and reproductive behavior

The human papilloma virus, 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 one's chances of contracting this disease and, therefore, developing cervical cancer. In addition, it has also been shown that women who do not have children or those who have children late in life have an increased risk for both ovarian and breast cancer.

Hormone replacement therapy

As women go through menopause, a physician may recommend hormone replacement therapy. This involves taking female hormones (called estrogen and progesterone) to control certain symptoms such as hot flashes and vaginal dryness that occur during this time of a woman's life. 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 was not fullyunderstood.

Family history

Certain cancers tend to occur more commonly among members of a family. Much of the time this seems to happens by chance, or is due to a common family habit such as cigarette smoking or extended sun exposure. However, certain cancers can occur in excess in some families due to a genetic predisposition that is passed from generation to generation. For example, if the BRCA1 gene is defective in a family, members of that family may have an increased risk to develop breast, colon, ovarian, or prostate cancer. Other defective genes can make persons susceptible to other types of cancer. Therefore, inheriting particular genes can increase a person's chance of developing cancer.

Occupational hazards

There is ample evidence 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 people who are smelters, gold miners and arsenic workers; leukemia is seen more frequently in people who work with glue and varnish; liver cancer is more prevalent in PVC manufacturers; and lung, bone, and bone marrow cancer is associated with radiologists and uranium miners.

Environment

High-frequency radiation has been shown to cause human cancer. Ultraviolet radiation from the sun accounts for a majority of melanoma cases. 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 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, increasing the risk for lung cancer. This risk is increased even further for a smoker who is exposed to asbestos over a period of time.

Causes and symptoms

Cancer is 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 (ACS) has established the following seven symptoms as possible warning signals 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

Other diseases can produce similar symptoms. However, it is important to have these symptoms checked as soon as possible, especially if they linger. The earlier a cancer is diagnosed and treated, the better the chance of it being cured. Many cancers, for example 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, a physician will begin with a complete medical history and a thorough physical examination. The doctor will examine different parts of the body in order to identify any variations from the normal size, feel, and texture of the organ or tissue. In addition to the physical exam, the doctor may order various 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.

A doctor may look for tumors by examining images of areas inside the body. The most common way to obtain these images is by using x rays. Other techniques used to examine the insides of the body include computed tomography (CT scan), magnetic resonance imaging (MRI), and ultrasonography.

The most definitive diagnostic test is a 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 an 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. Early detection means treatment is more likely to succeed. For example, the ACS recommends an annual mammogram (x ray of the breast) for women over the age of 40 years, to screen for breast cancer. It also recommends a sigmoidoscopy, in which a thin, lighted tube with a tiny camera is used to view the inside of the colon, every five years for people over the age of 50. This technique can assess the presence of colorectal cancer. Self-examinations for cancers of the breast, testes, mouth, and skin can also help in detecting tumors before the symptoms become serious.

Evolutions in molecular biology and the genetics of cancer have led to the development of several tests designed to assess one's risk of getting certain types of cancer. Genetic testing involves looking closely at certain genes that have been linked to particular cancers. As of 2001 there were many limitations to genetic testing. Tests could be uninformative and to a very small proportion of individuals tested. Additionally, concerns exist about insurance coverage and employment discrimination for someone who has an increased risk for cancer. As of 2001 these tests were reserved only for very specific individuals. A hereditary cancer clinic can help 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 recur- rence or spread 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. If the cancer is aggressive and a cure is not possible, then 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 an individual. The decision on which type of treatment is the most appropriate depends upon the type and location of the cancer and the extent to which it has already spread. A physician will also consider an affected person's age, sex, general health status, and personal treatment preferences. Treatment can be local, meaning that it affects cancer cells in the tumor and the surrounding area only. Surgery and radiation are local treatments. Treatment can also be systemic, meaning that the treatment travels through the bloodstream and affects cancer and other cells throughout the entire body. Chemotherapy, immunotherapy, and hormone therapy are examples of systemic treatments.

Surgery

Surgery can be used for many purposes:

• Treatment. Treatment of cancer by surgery involves removal of the tumor to cure the disease. This is typically done when the cancer is localized to a discrete area. Along with the cancer, some of the surrounding tissue is also removed to ensure that no cancer cells remain in the area. Since cancer usually spreads via the lymphatic system, lymph nodes near the tumor site may be removed for examination.
• Prevention. Preventive or prophylactic surgery involves removal of an abnormal-looking 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 colorectal cancer.
• Diagnosis. The most definitive tool for diagnosing cancer is a biopsy. Sometimes a biopsy can be performed by inserting a needle through the skin and aspirating a small amount of fluid or tissue. At other times the only way to obtain a tissue sample is through surgery.
• Cytoreductive surgery. This is a surgical procedure in which the surgeon removes as much of the cancer as possible. The remaining cancer cells are then treated with radiation therapy, chemotherapy, or both.
• Palliative surgery. This type of surgery is intended to relieve cancer symptoms or slow 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 technique may be used instead of surgery. It also may be utilized 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.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. The entire body is exposed to the drugs (systemic therapy) in an effort to destroy the hard-to-detect cancer cells that have spread and are circulating in the body. The cancer cells are affected more dramatically than 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, 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 technique, 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.

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 instances.

Bone marrow failure is a complication of chemotherapy. When high-dose chemotherapy is utilized, bone

Recommendations for cancer screening
Procedure	Frequency
SOURCE: U.S. Preventative Services Task Force, Dept. of Health and Human Services.
Chest x ray	Not recommended on a routine basis
Sputum cytology	Not recommended on a routine basis
Fecal occult blood	Yearly after age 50
testing (FOBT) or
sigmoidoscopy
Papanicolaou (Pap)	Every 3 years from onset of sexual activity to
smear	age 65
Mammography alone	Every 1–2 years at ages 50–69; starting at ages
or mammography	40–49 may be recommended if high-risk
and breast physical
examination

marrow 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 an affected person. Stem cells are immature cells that mature into blood cells. Transplanted stem cells replace the patient's stem cells that have been damaged or destroyed by chemotherapy or radiation. This procedure allows an individual to undergo very aggressive treatment for cancer. Those who receive BMT or PSCT have an increased risk of infection, bleeding, and other side effects due to the chemotherapy and radiation. Graft-versus-host dis- ease may also occur. This complication develops when the donated marrow reacts against the recipient's tissues. It can occur any time after the transplant. Drugs may be given to reduce the risk of graft-versus-host disease and to treat the problem if it occurs.

Immunotherapy

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 immunotherapy are variable but include flu- like symptoms, weakness, loss of appetite, and skin rash. These symptoms will subside after the treatment is completed.

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.

COMMON PATHOGENS AND THE CANCERS ASSOCIATED WITH THEM
Causative Agent	Type Of Cancers
Viruses
Papillomaviruses	Cancer of the cervix
Hepatitis B virus	Liver cancer
Hepatitis C virus	Liver cancer
Epstein-Barr virus	Burkitt's lymphoma
Cancers of the upper pharynx	Hodgkin's lymphoma, Non-Hodgkin's lymphoma, Gastric cancers
Human immunodeficiency virus (HIV)	Kaposi's sarcoma Lymphoma
Bacteria
Helicobacter pylori	Stomach cancer Lymphomas

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 they are used along with standard therapy, this is known as complementary therapy. Alternative therapy is considered dangerous because some of these unproven treatments might have life- threatening side effects. Additionally, persons who use alternative therapy may lose the opportunity to benefit from 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 before doing so.

Palliative care

Palliative care, which focuses on the terminally ill, is an extremely important aspect of care. Its goal is to prevent and relieve pain and suffering through symptom management, and addresses not only the physical, but the practical, emotional, and spiritual needs of patients, their families, and caregivers. By viewing dying as a natural process, palliative care helps facilitate what can be termed a "good" death, free from suffering and stress. Many patients and their families are unaware that suffering at the end of life is no longer necessary. Health care professionals can relieve a patient and their loved ones of much anxiety by informing them that appropriate symptom management is readily available.

Hospice care

Hospice care is the environment in which palliative care is given to terminally ill patients. Hospice care can be provided either at home, or in a home-like facility called a hospice. Hospice care focuses on providing the best possible palliative care for the patient until the patient dies.

Prognosis

Most cancers are curable if detected and treated in their early stages. The prognosis for a person with cancer is affected by many factors, particularly the type of cancer and stage of the cancer, the extent to which it has metastasized, and its aggressiveness. In addition, a person's age, general health status, and effectiveness of the treatment being pursued are important factors.

To help predict the outcome of cancer and the likeli- hood of recovery from the disease, five-year survival rates are used. In the United States, as of 2001, the five- year survival rate for all cancers combined was 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 people with cancer in a given population, it cannot be used to predict the course of cancer for an individual. No two people are exactly alike. The five-year survival rate does not account for differences in detection methods, types of treatments, additional illnesses, and personal behavior of the individual.

Health care team roles

Family physicians, internists, gynecologists, or pediatricians generally make an initial diagnosis of cancer. Other physicians, notable radiologists, and oncologists provide chemotherapeutic and radiologic treatment. Nurses provide emotional and educational support, home care, home hospice care, and case management. Counselors and psychologists may provide emotional support to patients and their families. Epidemiologists collect and maintain data related to cancer.

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 being used for treatment can also be suitable for prevention. For example, tamoxifen (Nolvadex) has been very effective against recurrence of 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 of, or prevent, head and neck cancers.

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KEY TERMS

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Benign—A growth that does not spread to other parts of the body. Recovery is favorable with treatment.

Biopsy—The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Bone marrow—Spongy material that fills the inner cavities of the bones. The progenitors of all the blood cells are produced in this bone marrow.

Carcinogen—Any substance capable of causing cancer by mutating a cell's DNA.

Chemotherapy—Treatment with anticancer drugs.

Epithelium—Layer of cells covering the body's surface and lining the internal organs and various glands.

Hormone therapy—Treatment of cancer by changing the hormonal environment, such as testosterone and estrogen.

Immunotherapy—Treatment of cancer by stimulating the body's immune system.

Malignant—A general term for cells that can break loose from an original tumor, invade, and then destroy other tissues and organs.

Metastasis—The spread of cancer from one part of the body to another.

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

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

Tumor—An abnormal growth resulting from a cell that lost its normal growth control restraints and started multiplying uncontrollably.

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

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L. Fleming Fallon, Jr., M.D., Dr.P.H.