NEL Molecular Genetics 689
Section20.4Gene Mutations and Cancer
Cancer is considered a genetic disease because it is always
associated with a mutation in the genetic sequence. However,
many different things can alter DNA, including viruses and
various environmental factors (Figure 2).Case StudyCase Study
normal mouse cells (growing in tissue culture) into cancerous
cells. The cancer-causing genes, called oncogenes, seemed to
turn on cell division. In their noncancerous state, oncogenes
are usually referred to as proto-oncogenes. Proto-oncogenes
may remain inactive or may perform some useful function
until they are triggered to become active oncogenes. Evidence
suggests that activation occurs in a number of steps, so a
single “hit” (mutation) does not immediately result in
cancerous cell divisions.
Further studies indicate that cancer-causing oncogenes are
present in normal strands of DNA. But if oncogenes are found
in normal cells, why do normal cells not become cancerous?
One current theory that has gained acceptance from the
scientific community suggests that the cancer gene has been
transposed (moved) to another gene site. Such transpositions
may have been brought about by environmental factors or
mutagenic chemicals or other agents.
Genes that direct the assembly of amino acids into proteins
are referred to as structural genes. Genes called regulator
genes act like a switch to turn “off” segments of the DNA
molecule, so that a gene is active only when and where its
gene product is needed. In very simple terms, when a
mutagen causes the oncogene to become separated from its
regulator gene, the cell may then be unable to turn the gene
"off" (Figure 3). This causes the cell to continue to divide at
an accelerated rate.32 %30 %10 %7 %5 %10 %3 % 1 %
2 %tobacco
diet
virusesenvironment
alcohol
sunlightSTDs
food additives
unknownFigure 2
Estimates of risk factors for cancer calculated in percentages.
Lifestyle choices related to diet and smoking can be linked
with over 60 % of cancer cases.Viruses inject foreign genetic information into cells,
disrupting the DNA that codes for cell division. Some viruses
that are linked to sexually transmitted diseases are known to
cause cancer. For example, women who have human
papillomavirus (HPV) have a greater incidence of cancer.
Environmental factors have been linked to other types of
cancer. Skin cancer, for example, has been linked with
ultraviolet radiation from the Sun. Exposure to harmful
chemicals in our environment can also cause cancer. A
number of cancer-causing substances can be found in
cigarettes.
Whatever the initial cause, scientists agree that all cancers
are related to mutations. Usually, it takes more than one
mutation to trigger a malignant growth. This is why cancer
usually occurs more frequently in older people.
Two lines of evidence indicate that cancer results from
mutations. First, cancer cells often display nitrogen base
substitution, or the movement of genetic material from one
part of the chromosome to another. Second, many known
mutagens are also known to cause cancer. X-rays, ultraviolet
radiation, and mutagenic chemicals can induce cancer.
In 1982, molecular biologists were able to provide additional
evidence to support the hypothesis that cancer could be
traced to genetic mutations. Segments of chromosomes
extracted from cancerous mice were used to transformDNA moleculeregulator gene
structural geneDNA molecule broken apartregulator gene
structural generadiationenzymes repair DNA moleculeFigure 3
Mutagenic agents may cause the separation of the regulator
and structural genes. If the structural gene codes for a protein
involved in controlling cell division, this separation can lead to
cancer.