Cancer is a complex family of diseases, and carcinogenesis, the events that turn a normal cell in
the body into a cancer cell, is a complex multistep process. From a clinical point of view, cancer
is a large group of diseases, perhaps up to a hundred or more, that vary in their age of onset,
rate of growth, state of cellular differentiation, diagnostic detectability, invasiveness, metastatic
potential, response to treatment, and prognosis. From a molecular and cell biological point of
view, however, cancer may be a relatively small number of diseases caused by similar molecular
defects in cell function resulting from common types of alterations to a cell’s genes. Ultimately,
cancer is a disease of abnormal gene expression. There are a number of mechanisms by which
this altered gene expression occurs. These mechanisms may occur via a direct insult to DNA,
such as a gene mutation, translocation, amplification, deletion, loss of heterozygosity, or via a
mechanism resulting from abnormal gene transcription or translation. The overall result is an
imbalance of cell replication and cell death in a tumor cell population that leads to an expansion
of tumor tissue. In normal tissues, cell proliferation and cell loss are in a state of equilibrium.
Cancer is a leading cause of death in the Western world. In the United States and a number
of European countries, cancer is the secondleading killer after cardiovascular disease, although
in the United States since 1999 cancer has surpassed heart disease as the number one
cause of death in people younger than 85.1 Over 1.3 million new cases of cancer occur in the
United States each year, not including basal cell and squamous cell skin cancers, which add another
1 million cases annually. These skin cancers are seldom fatal, do not usually metastasize, and
are curable with appropriate treatment, so they are usually considered separately. Melanoma,
by contrast, is a type of skin cancer that is more dangerous and can be fatal, so it is considered
with the others. The highest mortality rates are seen with lung, colorectal, breast, and prostate
cancers (Fig. 1–1). Over 570,000 people die each year in the United States from these and
other cancers. More people die of cancer in 1 year in the United States than the number of
people killed in all the wars in which the United States was involved in the twentieth century
In many cases the causes of cancer aren’t clearly defined, but both external (e.g., environmental
chemicals and radiation) and internal (e.g., immune system defects, genetic predisposition)
factors play a role (see Chapter 2). Clearly, cigarette smoking is a major causative factor.
These causal factors may act together to initiate (the initial genetic insult) and promote (stimulation
of growth of initiated cells) carcinogenesis. Often 10 to 20 years may pass before an
initiated neoplastic cell grows into a clinically detectable tumor.
Although cancer can occur at any age, it is usually considered a disease of aging. The average
age at the time of diagnosis for cancer of all sites is 67 years, and about 76% of all cancers are diagnosed at age 55 or older. Although cancer is relatively rare in children, it is the secondleading cause of death in children ages 1–14. In this age group leukemia is the most common cause of death, but other cancers such as osteosarcoma, neuroblastoma, Wilms’ tumor (a kidney cancer), and lymphoma also occur. Over eight million Americans alive today have had some type of cancer. Of these, about half are considered cured. It is estimated that about one in three people now living will develop some type of cancer. There has been a steady rise in cancer death rates in the United States during the past 75 years. However, the major reason why cancer accounts for a higher proportion of deaths now than it did in the past is that today more people live long enough to get cancer, whereas earlier in the twentieth century more people died of infectious disease and other causes. For example, in 1900 life expectancy was 46 years for men and 48 years for women. By 2000, the expectancy had risen to age 74 for men and age 80 for women. Thus, even though the overall death rates due to cancer have almost tripled since
1930 for men and gone up over 50% for women,
