Essential Cell Biology 5th edition

720 CHAPTER 20 Cell Communities: Tissues, Stem Cells, and Cancer
the cervical epithelium with certain subtypes of a common virus called
human papillomavirus. These viruses are transmitted through sexual
intercourse and can sometimes, if one is unlucky, provoke uncontrolled
proliferation of the infected cells. Knowing this, we can attempt to prevent
the cancer by preventing the infection—for example, by vaccination
against the relevant papillomaviruses. Such a vaccine is now available,
conferring a high level of protection if given to young people before they
become sexually active.
In the great majority of human cancers, however, viruses do not appear
to play a part: as we will see, cancer is not an infectious disease. But epidemiology
reveals that other factors increase the risk of cancer. Obesity
is one such factor. Smoking tobacco is another: tobacco smoke is not
only responsible for the great majority of lung cancer cases, but it also
raises the incidence of several other cancers, such as those of the bladder.
By stopping the use of tobacco, we could prevent about 30% of all
cancer deaths. No other single policy or treatment is known that would
have such a dramatic impact on the number of cancer deaths.
As we will explain, although environmental factors affect the incidence of
cancer and are critical for some forms of the disease, it would be wrong
to conclude that they are the only cause of cancers. No matter how hard
we try, healthy living alone will not reduce our risk of cancer to zero.
Cancers Develop by an Accumulation of Somatic
Mutations
Cancer is fundamentally a genetic disease: it arises as a consequence of
pathological changes in the information carried by DNA. It differs from
other genetic diseases in that the mutations underlying cancer are mainly
somatic mutations—those that occur in individual somatic cells of the
body—as opposed to germ-line mutations, which are handed down via
the germ cells from which the entire multicellular organism develops.
Most of the identified agents known to contribute to the causation of
cancer, including ionizing radiation and most chemical carcinogens, are
mutagens: they cause changes in the nucleotide sequence of DNA. But
even in an environment that is free of tobacco smoke, radioactivity, and
all the other external mutagens that worry us, mutations will occur spontaneously
as a result of the fundamental limitations on the accuracy of
DNA replication and DNA repair (discussed in Chapter 6). In fact, environmental
carcinogens other than tobacco smoke probably account for only
a small fraction of the mutations responsible for cancer, and elimination
of all these external risk factors would still leave us prone to the disease.
Although DNA is replicated and repaired with great accuracy, an average
of one mistake slips by for every 10 9 or 10 10 nucleotides copied, as we
discuss in Chapter 6. This means that spontaneous mutations occur at an
estimated rate of about 10 –6 or 10 –7 mutations per gene per cell division,
even without encouragement by external mutagens. About 10 16 cell divisions
take place in a human body in the course of an average lifetime;
thus, every single gene is likely to have acquired a mutation on more
than 10 9 separate occasions in any individual. From this point of view,
the problem of cancer seems to be not why it occurs, but why it occurs
so infrequently.
The explanation is that most mutations do not contribute to cancer—even
though they may happen to be found in a cancer cell; these mutations are
called passenger mutations. At the same time, for those mutations that do
promote cancer, a single mutation is generally not sufficient. Precisely
how many of these cancer-critical, or driver, mutations are required is still
a matter of debate, but for most full-blown cancers it could be at least