Cancer is a renegade system of growth that originates within a patient’s biosystem more commonly known as the human body. There are many different types of cancers, but all share one hallmark characteristic: unchecked growth that progresses toward limitless expansion. It is difficult to imagine anyone who has not heard of this illness. Most people have been affected because either they or their loved ones or friends are cancer survivors. Because cancer is so prevalent, people have many questions about its biology, detection, diagnosis, possible causes and strategies for prevention.
Cancer can originate almost anywhere in the body. Carcinomas, the most common types of cancer, arise from the cells that cover external and internal body surfaces. Lung, breast, and colon are the most frequent cancers of this type in the United States. Sarcomas are cancers arising from cells found in the supporting tissues of the body such as bone, cartilage, fat, connective tissue, and muscle. Lymphomas are cancers that arise in the lymph nodes and tissues of the body’s immune system. Leukemias are cancers of the immature blood cells that grow in the bone marrow and tend to accumulate in large numbers in the bloodstream.
Cancer arises from a loss of normal growth control. In normal tissues, the rates of new cell growth and old cell death are kept in balance. In cancer, this balance is disrupted. This disruption can result from uncontrolled cell growth or loss of a cell’s ability to undergo cell suicide by a process called “apoptosis.” Apoptosis or “cell suicide” is the mechanism by which old or damaged cells normally self-destruct.
During the development of skin cancer, the normal balance between cell division and cell loss is disrupted. The basal cells now divide faster than is needed to replenish the cells being shed from the surface of the skin. Each time one of these basal cells divides, the two newly formed cells will often retain the capacity to divide, thereby leading to an increase in the total number of dividing cells.
This gradual increase in the number of dividing cells creates a growing mass of tissue called a “tumor” or “neoplasm.” If the rate of cell division is relatively rapid and no “suicide” signals are in place to trigger cell death, the tumor will grow quickly in size; if the cells divide more slowly, tumor growth will be slower. But regardless of the growth rate, tumors ultimately increase in size because new cells are being produced in greater numbers than needed. As more and more of these dividing cells accumulate, the normal organization of the tissue gradually becomes disrupted.
Cancers are capable of spreading throughout the body by two mechanisms: invasion and metastasis. Invasion refers to the direct migration and penetration by cancer cells into neighboring tissues. Metastasis refers to the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then invade normal tissues elsewhere in the body.
Depending on whether or not they can spread by invasion and metastasis, tumors are classified as being either benign or malignant. Benign tumors are tumors that cannot spread by invasion or metastasis; hence, they only grow locally. Malignant tumors are tumors that are capable of spreading by invasion and metastasis. By definition, the term “cancer” applies only to malignant tumors.
A malignant tumor, a “cancer,” is a more serious health problem than a benign tumor because cancer cells can spread to distant parts of the body. For example, a melanoma (a cancer of pigmented cells) arising in the skin can have cells that enter the bloodstream and spread to distant organs such as the liver or brain. Cancer cells in the liver would be called metastatic melanoma not liver cancer. Metastases share the name of the original (“primary”) tumor. Melanoma cells growing in the brain or liver can disrupt the functions of these vital organs and so are potentially life-threatening.
Detecting cancer early can affect the outcome of the disease for some cancers. When cancer is found, a doctor will determine what type it is and how fast it is growing. He or she will also determine whether cancer cells have invaded nearby healthy tissue or spread (metastasized) to other parts of the body. In some cases, finding cancer early may decrease a person’s risk of dying from the cancer. For this reason, improving our methods for early detection is currently a high priority for cancer researchers.
Some people visit the doctor only when they feel pain or when they notice changes like a lump in the breast or unusual bleeding or discharge, but don’t wait until then to be checked because early cancer may not have any symptoms. That is why screening for some cancers is important, particularly as you get older. Screening methods are designed to check for cancer in people with no symptoms.
A screening technique called the Pap test (or Pap smear) allows early detection of cancer of the cervix, the narrow portion of the uterus that extends down into the upper part of the vagina. In this procedure, a doctor uses a small brush or wooden scraper to remove a sample of cells from the cervix and upper vagina. The cells are placed on a slide and sent to a laboratory where a microscope is used to check for abnormalities. Since the 1930s, early detection using the Pap test has helped lower the death rate from cervical cancer more than 75 percent. Should abnormalities be found, an additional test may be necessary. There are now 13 high-risk types of human papillomaviruses (HPV) recognized as the major causes of cervical cancer. The U.S. Food and Drug Administration has approved an HPV test that can identify their presence in a tissue sample. This test can detect the viruses even before there are any conclusive visible changes to the cervical cells.
Breast cancer can sometimes be detected in its early stages using a mammogram, an X-ray of the breast. Mammography is most beneficial for women as they age and undergo menopause. Mammography is a screening tool that can detect the possible presence of an abnormal tissue mass. By itself, it is not accurate enough to provide definitive proof of either the presence or the absence of breast cancer. If a mammogram indicates the presence of an abnormality, further tests must be done to determine whether breast cancer actually is present.
The U.S. Food and Drug Administration has approved the PSA test along with a digital rectal exam to help detect prostate cancer in men age 50 and older . Doctors often use the PSA test and DRE as prostate cancer screening tests; together, these tests can help doctors detect prostate cancer in men who have no symptoms of the disease. Most men with an elevated PSA test though turn out not to have cancer; only 25 to 30 percent of men who have a biopsy due to elevated PSA levels actually have prostate cancer so researchers are working hard to find new clues. Experts are trying to develop better blood tests that might alert people to malignancies while the cancers are still in their early stages, for example, several new blood tests for ovarian or prostate cancer are under development.
A procedure called a fecal occult blood test (FOBT) detects invisible amounts of blood in the feces, a possible sign of several disorders including colon cancer. The test is painless and can be done at home or in the doctor’s office along with a rectal exam. With an application stick, a dab of a stool specimen is smeared on a chemically-treated card, which is tested in a laboratory for evidence of blood. If blood is confirmed in the stool, more elaborate tests may be performed to find the source of the bleeding. Some other options include sigmoidoscopy and colonoscopy. The former exam uses a lighted instrument called a sigmoidoscope to find precancerous or cancerous growths in the rectum and lower colon. The latter exam uses a lighted instrument called a colonoscope to find precancerous or cancerous growths throughout the colon including the upper part.
To diagnose the presence of cancer, a doctor must look at a sample of the affected tissue under the microscope. Hence, when preliminary symptoms, Pap test, mammogram, PSA test, FOBT, or colonoscopy indicate the possible existence of cancer, a doctor must then perform a biopsy, which is the surgical removal of a small piece of tissue for microscopic examination. (For leukemias, a small blood sample serves the same purpose.) This microscopic examination will tell the doctor whether a tumor is actually present and, if so, whether it is malignant (i.e., cancer) or benign. In addition, microarrays may be used to determine which genes are turned on or off in the sample or proteomic profiles may be collected for an analysis of protein activity. This information will help doctors to make a more accurate diagnosis and may even help with treatment planning.
Cancer tissue has a distinctive appearance under the microscope. Among the traits the doctor looks for are a large number of irregularly-shaped dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, loss of normal tissue organization, and a poorly defined tumor boundary.
Instead of finding a benign or malignant tumor, microscopic examination of a biopsy specimen will sometimes detect a condition called “hyperplasia.” Hyperplasia refers to tissue growth based on an excessive rate of cell division leading to a larger than usual number of cells. Nonetheless, cell structure and the orderly arrangement of cells within the tissue remain normal, and the process of hyperplasia is potentially reversible. Hyperplasia can be a normal tissue response to an irritating stimulus. An example of hyperplasia is a callus that may form on your hand when you first learn to swing a tennis racket or golf club.
In addition to hyperplasia, microscopic examination of a biopsy specimen can detect another type of noncancerous condition called “dysplasia.” Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure. Often such cells revert back to normal behavior, but occasionally they gradually become malignant. Because of their potential for becoming malignant, areas of dysplasia should be closely monitored by a health professional as sometimes they need treatment.
The most severe cases of dysplasia are sometimes referred to as “carcinoma in situ.” In Latin, the term “in situ” means “in place,” so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location. However, carcinoma in situ may develop into an invasive, metastatic malignancy and, therefore, is usually removed surgically, if possible.
Microscopic examination also provides information regarding the likely behavior of a tumor and its responsiveness to treatment. Cancers with highly abnormal cell appearance and large numbers of dividing cells tend to grow more quickly, spread to other organs more frequently, and be less responsive to therapy than cancers whose cells have a more normal appearance. Based on these differences in microscopic appearance, doctors assign a numerical “grade” to most cancers. In this grading system, a low number grade (grade 1 or 2) refers to cancers with fewer cell abnormalities than those with higher numbers (grade 3 or 4).
After cancer has been diagnosed, doctors ask the following three questions to determine how far the disease has progressed:
- How large is the tumor and how deeply has it invaded surrounding tissues?
- Have cancer cells spread to regional lymph nodes?
- Has the cancer spread (metastasized) to other regions of the body?
Based on the answers to these questions, the cancer is assigned a “stage.” A patient’s chances for survival are better when cancer is detected at a lower stage.
Cancer is often perceived as a disease that strikes for no apparent reason. While scientists don’t yet know all the reasons, many of the causes of cancer have already been identified. Besides intrinsic factors such as heredity, diet, and hormones, scientific studies point to key extrinsic factors that contribute to the cancer’s development: chemicals (e.g., smoking), radiation, and viruses or bacteria.
In theory, differences in heredity or environmental risk factors might be responsible for the different cancer rates observed in different countries. Studies on people who have moved from one country to another suggest that exposure to risk factors for cancer varies by geographic location. For example, in Japan, the rate of colon cancer is lower, and the rate of stomach cancer is higher than in the United States. But this difference has been found to gradually disappear in Japanese families that have moved to the United States. This suggests that the risk of developing the two kinds of cancer is not determined primarily by heredity. The change in risk for cancer for Japanese families could involve cultural, behavioral, or environmental factors predominant in one location and not in the other.
Among the various factors that can cause cancer, tobacco smoking is the greatest public health hazard. Cigarette smoke contains more than two dozen different chemicals capable of causing cancer. Cigarette smoking is the main cause of lung cancer and contributes to many other kinds of cancer as well including cancer of the mouth, larynx, esophagus, stomach, pancreas, kidney, and bladder. Current estimates suggest that smoking cigarettes is responsible for at least one out of every three cancer deaths, making it the largest single cause of death from cancer. Other forms of tobacco use also can cause cancer. For example, cigars, pipe smoke, and smokeless tobacco can cause cancer of the mouth.
Some atoms give off radiation, which is energy that travels through space. Prolonged or repeated exposure to certain types of radiation can cause cancer. Cancer caused by the sun’s ultraviolet radiation is most common in people who spend long hours in strong sunlight. Ultraviolet radiation from sunlight is a low-strength type of radiation. Effective ways to protect against ultraviolet radiation and to prevent skin cancer are to avoid going into strong, direct sunlight and to wear protective clothing. Sunscreen lotions reduce the risk of some forms of skin cancers.
Increased rates of cancer also have been detected in people exposed to high-strength forms of radiation such as X-rays or radiation emitted from unstable atoms called radioisotopes. Because these two types of radiation are stronger than ultraviolet radiation, they can penetrate through clothing and skin into the body. Therefore, high-strength radiation can cause cancer of internal body tissues. Examples include cancer caused by nuclear fallout from atomic explosions and cancers caused by excessive exposure to radioactive chemicals.
Chemicals and radiation that are capable of triggering the development of cancer are called “carcinogens.” Carcinogens act through a multistep process that initiates a series of genetic alterations (“mutations”) and stimulates cells to proliferate. A prolonged period of time is usually required for these multiple steps. There can be a delay of several decades between exposure to a carcinogen and the onset of cancer. For example, young people exposed to carcinogens from smoking cigarettes generally do not develop cancer for 20 to 30 years. This period between exposure and onset of disease is the lag time.
In addition to chemicals and radiation, a few viruses also can trigger the development of cancer. In general, viruses are small infectious agents that cannot reproduce on their own, but instead enter into living cells and cause the infected cell to produce more copies of the virus. Like cells, viruses store their genetic instructions in large molecules called nucleic acids. In the case of cancer viruses, some of the viral genetic information carried in these nucleic acids is inserted into the chromosomes of the infected cell, and this causes the cell to become malignant.
Only a few viruses that infect human cells actually cause cancer. Included in this category are viruses implicated in cervical cancer, liver cancer, and certain lymphomas, leukemias, and sarcomas. Susceptibility to these cancers can sometimes be spread from person to person by infectious viruses, although such events account for only a very small fraction of human cancers. For example, the risk of cervical cancer is increased in women with multiple sexual partners and is especially high in women who marry men whose previous wives had this disease. Transmission of the human papillomavirus (HPV) during sexual relations appears to be involved.
People who develop AIDS after being infected with the human immunodeficiency virus (HIV) are at high risk for developing a specific type of cancer called Kaposi’s sarcoma. Kaposi’s sarcoma is a malignant tumor of blood vessels located in the skin. This type of cancer is not directly caused by HIV infection. Instead, HIV causes an immune deficiency that makes people more susceptible to viral infection. Infection by a virus called KSHV (Kaposi’s sarcoma-associated herpes virus) then appears to stimulate the development of Kaposi’s sarcoma.
Viruses are not the only infectious agents that have been implicated in human cancer. The bacterium Helicobacter pylori, which can cause stomach ulcers, has been associated with the development of cancer, so people infected with H. pylori are at increased risk for stomach cancer. Research is underway to define the genetic interactions between this infectious agent and its host tissues that may explain why cancer develops.
Cancer is not considered an inherited illness because most cases of cancer, perhaps 80 to 90 percent, occur in people with no family history of the disease. However, a person’s chances of developing cancer can be influenced by the inheritance of certain kinds of genetic alterations. These alterations tend to increase an individual’s susceptibility to developing cancer in the future. For example, about 5 percent of breast cancers are thought to be due to inheritance of particular form(s) of a “breast cancer susceptibility gene.”
Because a number of mutations usually must occur for cancer to arise, the chances of developing cancer increase as a person gets older because more time has been available for mutations to accumulate. For example, a 75-year-old person is a hundred times more likely to develop colon cancer than a 25-year-old. Because people are living longer today than they did 50 to 100 years ago, they have a longer exposure time to factors that may promote gene changes linked to cancer.
Cancer may begin because of the accumulation of mutations involving oncogenes, tumor suppressor genes, and DNA repair genes. For example, colon cancer can begin with a defect in a tumor suppressor gene that allows excessive cell proliferation. The proliferating cells then tend to acquire additional mutations involving DNA repair genes, other tumor suppressor genes, and many other growth-related genes. Over time, the accumulated damage can yield a highly malignant, metastatic tumor. In other words, creating a cancer cell requires that the brakes on cell growth (tumor suppressor genes) be released at the same time that the accelerators for cell growth (oncogenes) are being activated.
In addition to all the molecular changes that occur within a cancer cell, the environment around the tumor changes dramatically as well. The cancer cell loses receptors that would normally respond to neighboring cells that call for growth to stop. Instead, tumors amplify their own supply of growth signals. They also flood their neighbors with other signals called cytokines and enzymes called proteases. This action destroys both the basement membrane and surrounding matrix, which lies between the tumor and its path to metastasis–a blood vessel or duct of the lymphatic system.
Since exposure to carcinogens (cancer-causing agents) is responsible for triggering most human cancers, people can reduce their cancer risk by taking steps to avoid such agents. Hence the first step in cancer prevention is to identify the behaviors or exposures to particular kinds of carcinogens and viruses that represent the greatest cancer hazards.
As the single largest cause of cancer death, the use of tobacco products is implicated in roughly one out of every three cancer deaths. Cigarette smoking is responsible for nearly all cases of lung cancer, and has also been implicated in cancer of the mouth, larynx, esophagus, stomach, pancreas, kidney, and bladder. Pipe smoke, cigars, and smokeless tobacco are risky as well. Avoiding tobacco is therefore the single most effective lifestyle decision any person can make in attempting to prevent cancer.
While some sunlight is good for health, skin cancer caused by excessive exposure to sunlight is not among the sun’s benefits. Because some types of skin cancer are easy to cure, the danger posed by too much sunlight is perhaps not taken seriously enough. It is important to remember that a more serious form of skin cancer, called melanoma, is also associated with excessive sun exposure. Melanomas are potentially lethal tumors. Risk of melanoma and other forms of skin cancer can be significantly reduced by avoiding excessive exposure to the sun, using sunscreen lotions, and wearing protective clothing to shield the skin from ultraviolet radiation.
Drinking excessive amounts of alcohol is linked to an increased risk for several kinds of cancer, especially those of the mouth, throat, and esophagus. The combination of alcohol and tobacco appears to be especially dangerous. For example, in heavy smokers or heavy drinkers, the risk of developing cancer of the esophagus is roughly 6 times greater than that for nonsmokers/nondrinkers. But in people who both smoke and drink, the cancer risk is more than 40 times greater than that for nonsmokers/nondrinkers. Clearly the combination of alcohol and tobacco is riskier than would be expected by just adding the effects of the two together.
Studies suggest that differences in diet may also play a role in determining cancer risk. Unlike clear-cut cancer risk factors such as tobacco, sunlight, and alcohol, dietary components that influence cancer risk have been difficult to determine. Limiting fat consumption and calorie intake appears to be one possible strategy to decrease risk for some cancers, because people who consume large amounts of meat, which is rich in fat, and large numbers of calories exhibit an increased cancer risk especially for colon cancer.
In contrast to factors such as fat and calories, which appear to increase cancer risk, other dietary components may decrease cancer risk. The most compelling evidence has been obtained for fruits and vegetables, whose consumption has been strongly correlated with a reduction in cancer risk. Although the exact chemical components in these foods that are responsible for a protective effect are yet to be identified, eating five to nine servings of fruits and vegetables each day is recommended by many groups.
Actions can also be taken to avoid exposure to the small number of viruses that have been implicated in human cancers. A good example is the human papillomavirus (HPV). Of the more than 100 types of HPVs, over 30 types can be passed from one person to another through sexual contact. Among these, there are 13 high-risk types recognized as the major cause of cervical cancer. Having many sexual partners is a risk factor for infection with these high-risk HPVs, which can, in turn, increase the chance that mild cervical abnormalities will progress to more severe ones or to cervical cancer.
Because people spend so much time at work, potential carcinogens in the work environment are studied carefully. Some occupational carcinogens have been identified because coworkers exposed to the same substances have developed a particular kind of cancer at increased frequency. For example, cancer rates in construction workers who handle asbestos have been found to be 10 times higher than normal.
A common misconception arises from news stories suggesting we are experiencing a cancer “epidemic.” This only appears to be the case because the number of new cancer cases reported is rising as the population is both expanding and aging. Older people are more likely to develop cancer; however, this trend is offset by new births, which are also increasing, and cancer is rare among the young. So as more and more members of a 75-million-strong “baby-boomer” cohort begin shifting en masse to older, more cancer-prone ages, the number of new cancer cases is expected to increase in the next several decades. But since the birth rate is also expected to increase, the cancer rate may either stay the same or, perhaps, decline.
