For most Americans, the real issues associated with cancer are personal. More than 8 million Americans alive today have a history of cancer (National Cancer Institute, 1998; Rennie, 1996). In fact, cancer is the second leading cause of death in the United States, exceeded only by heart disease.
Who are these people who develop cancer and what are their chances for surviving it? Scientists measure the impact of cancer in a population by looking at a combination of three elements: (1) the number of new cases per year per 100,000 persons (incidence rate), (2) the number of deaths per 100,000 persons per year (mortality rate), and (3) the proportion of patients alive at some point after their diagnosis of cancer (survival rate). Data on incidence, mortality, and survival are collected from a variety of sources. For example, in the United States there are many statewide cancer registries and some regional registries based on groups of counties, many of which surround large metropolitan areas. Some of these population based registries keep track of cancer incidence in their geographic areas only; others also collect follow-up information to calculate survival rates.
In 1973, the National Cancer Institute began the Surveillance, Epidemiology, and End Results Program (SEER) to estimate cancer incidence and patient survival in the United States. SEER collects cancer incidence data in 11 geographic areas and two supplemental registries, for a combined population of approximately 14 percent of the entire U.S. population. Data from SEER are used to track cancer incidence in the United States by primary cancer site, race, sex, age, and year of diagnosis. For example, Figure 7 shows SEER data for the age-adjusted cancer incidence rates for the 10 most common sites for Caucasian and African-American males and females for the period 1987-1991.
Cancer among children is relatively rare. SEER data from 1991 showed an incidence of only 14.1 cases per 100,000 children under age 15. Nevertheless, after accidents, cancer is the second leading cause of childhood death in the United States. Leukemias (4.3 per 100,000) and cancer of the brain and other nervous system organs (3.4 per 100,000) account for more than one-half of the cancers among children.
Everyone is at some risk of developing cancer. Cancer researchers use the term lifetime risk to indicate the probability that a person will develop cancer over the course of a lifetime. In the United States, men have a 1 in 2 lifetime risk of developing cancer, and women have a 1 in 3 risk.
For a specific individual, however, the risk of developing a particular type of cancer may be quite different from his or her lifetime risk of developing any type of cancer. Relative risk compares the risk of developing cancer between persons with a certain exposure or characteristic and persons who do not have this exposure or characteristic. For example, a person who smokes has a 10-to-20-fold-higher relative risk of developing lung cancer compared with a person who does not smoke. This means that a smoker is 10 to 20 times more likely to develop lung cancer than a nonsmoker.
Scientists rely heavily on epidemiology to help them identify factors associated with the development of cancer. Epidemiologists look for factors that are common to cancer victims' histories and lives and evaluate these factors in the light of current understandings of the disease. With enough study, researchers may assemble evidence that a particular factor "causes" cancer, that is, that exposure to it increases significantly the probability of the disease developing. Although this information cannot be used to predict what will happen to any one individual exposed to this risk factor, it can help people make choices that reduce their exposure to known carcinogens (cancer-causing agents) and increase the probability that if cancer develops, it will be detected early (for example, by getting regular check-ups and participating in cancer screening programs).
Figure 7 - Age-Adjusted Cancer Incidence Rates, 1987-1991 D
As noted above, hereditary factors also can contribute to the development of cancer. Some people are born with mutations that directly promote the unrestrained growth of certain cells or the occurrence of more mutations. These mutations, such as the mutation identified in the 1980s that causes retinoblastoma, confer a high relative cancer risk. Such mutations are rare in the population, however, accounting for the development of fewer than 5 percent of the cases of fatal cancer.
Hereditary factors also contribute to the development of cancer by dictating a person's general physiological traits. For example, a person with fair skin is more susceptible to the development of skin cancer than a person with a darker complexion. Likewise, a person whose body metabolizes and eliminates a particular carcinogen relatively inefficiently is more likely to develop types of cancer associated with that carcinogen than a person who has more efficient forms of the genes involved in that particular metabolic process. These inherited characteristics do not directly promote the development of cancer; each person, susceptible or not, still must be exposed to the related environ-mental carcinogen for cancer to develop. Nevertheless, genes probably do contribute in some way to the vast majority of cancers.
One question often asked about cancer is, "How many cases of cancer would be expected to occur naturally in a population of individuals who somehow had managed to avoid all environmental carcinogens and also had no mutations that predisposed them to developing cancer?" Comparing populations around the world with very different cancer patterns has led epidemiologists to suggest that perhaps only about 25 percent of all cancers are "hard core"—that is, would develop anyway, even in a world free of external influences. These cancers would occur simply because of the production of carcinogens within the body and because of the random occurrence of unrepaired genetic mistakes.
Although cancer continues to be a significant health issue in the United States, a recent report from the American Cancer Society (ACS), National Cancer Institute (NCI), and Centers for Disease Control and Prevention (CDC) indicates that health officials are making progress in controlling the disease. In a news bulletin released on 12 March 1998, the ACS, NCI, and CDC announced the first sustained decline in the cancer death rate, a turning point from the steady increase observed throughout much of the century. The report showed that after increasing 1.2 percent per year from 1973 to 1990, the incidence for all cancers combined declined an average of 0.7 percent per year from 1990 to 1995. The overall cancer death rate also declined by about 0.5 percent per year across this period.
The overall survival rate for all cancer sites combined also continues to increase steadily, from 49.3 percent in 1974-1976 to 53.9 percent in 1983-1990 (Figure 8). In some cases—for example, among children age 15 and younger—survival rates have increased dramatically.
What explanation can we offer for the steady increase in survival rates among cancer patients? One answer likely is the improvements scientists have made in cancer detection.
Figure 8 - Five-Year Relative Survival Rates for Selected Cancer Sites, All Races D
These improvements include a variety of new imaging techniques as well as blood and other tests that can help physicians detect and diagnose cancer early. Although many Americans regularly watch for the early symptoms of cancer, by the time symptoms occur many tumors already have grown quite large and may have metastasized. Likewise, many cancers have no symptoms. Clearly, great effort is needed to educate Americans that cancer screening (checking for cancer in people with no symptoms) is key to early detection.
Another explanation for increased survival is improved treatment. Today, the traditional workhorses of cancer treatment—surgery, radiation, and chemotherapy—are being used in ways that are increasingly specific to the type of cancer involved. In fact, many cases of cancer now are being fully cured.
But is this the best we can do? What will the future bring? Hellman and Vokes, in their 1996 article in Scientific American, note that war often serves as a metaphor for cancer research. In 1971, two days before Christmas, President Richard M. Nixon signed the National Cancer Act, committing the United States to a "war" on cancer. Although the analogy is not perfect, Hellman and Vokes suggest that it can help us understand our current position with respect to cancer prevention, detection, and treatment. Looking at the "map" of cancer research after almost 30 years of "war," we can see that we have made some modest advances. But these successes do not reveal the tremendous developments that lie ahead of us by virtue of the new, strategic position we have achieved. In fact, most scientists expect that our newly gained understanding of the molecular basis of cancer will eventually give rise to a whole generation of exciting new techniques, not only for detecting and treating cancer but also for preventing it.
A key area of interest lies in learning how to exploit the molecular abnormalities of cancer cells to bring about their destruction. For example, understanding the role of oncogenes in the development of cancer suggests new targets for anticancer therapies. Some drug companies are working on drugs designed to shut down abnormal receptor proteins. Other potential targets are the aberrant proteins within the cytoplasm that transmit stimulatory signals even without being stimulated by surface receptors.
As in the case of oncogenes, a better understanding of the role of tumor-suppressor genes in preventing runaway cell division may help scientists develop new therapies directed at these genes. For example, various studies have shown that introducing a normal tumor-suppressor gene into a cell can help restore the cell to normalcy. Similarly, a therapy capable of restoring a cell's capacity for apoptosis would improve significantly the effectiveness of current cancer treatments. Even telomerase represents an important potential target for scientists looking for new and more powerful treatments for cancer. If telomerase could be blocked in cancer cells, their telomeres would continue to shorten with each division until their own proliferation pushed them into a genetic crisis and death.
One bold new research initiative that offers significant promise is the Cancer Genome Anatomy Project (CGAP). The project's goal is to identify all the genes responsible for the establishment and growth of human cancer. The work is based on a simple concept: Although almost every cell in the body contains the full set of human genes, only about one-tenth of them are expressed in any particular type of cell. Thus, different types of cells—for example, muscle cells and skin cells—can be distinguished by their patterns of gene expression.
Establishing for a particular cell the repertoire of genes expressed, together with the amount of normal or altered gene product produced by each expressed gene, yields a powerful "fingerprint" or "signature" for that cell type. Not unexpectedly, during the transformation of a normal cell to a cancer cell, this signature changes. Some changes are quantitative. That is, gene A may be expressed in both cells, but at greatly different levels, or it may be expressed in one cell but not the other. Other changes are qualitative: Gene B may be expressed at the same level in both cells, but produce an altered product in the cancerous cell.
Copyright | Credits | Accessibility