How Genes Cause Cancer
How do genes cause cancer?
To understand the mechanisms of how genes cause cancer, it is important to review
some basic genetic concepts.
Genes come in pairs, and work together to make a protein product. One copy of the
gene pair comes from the mother. The other copy is inherited from the father. Eggs
and sperm are called germ cells. When a change or mutation in a gene is present in the germ cells, it is referred
to as a germline mutation. When a germline mutation is inherited, it is present in all body cells from birth.
On the other hand, mutations that we are not born with, but that happen by chance
over time, are said to be acquired. Acquired mutations are not present in all cells of the body, are not inherited,
and are not passed down to our children. Most human cancers are thought to be caused
by acquired mutations. Germline mutations are involved in a small percentage of cases.
The formation of tumors is caused by cell growth that gets out of control. In the
human genome, there are many different types of genes that control cell growth in
a very systematic, precise way. When these genes have an error in their DNA code,
they may not work properly. They are said to be altered or mutated. In most cases of cancer, many mutations must happen in one after another
in different genes in a specific group of cells over time to cause malignancy. The
different types of genes that, when mutated, can lead to the development of cancer
are described below. Remember, it usually takes mutations in several of these genes
for a person to develop cancer. What specifically causes mutations to happen one after
another in these genes is largely unknown. Mutations can be caused by carcinogens
(environmental factors known to increase the risk of cancer). The development of mutations
is also a natural part of the aging process.
These are altered forms of genes known as proto-oncogenes. Proto-oncogenes are responsible
for promoting cell growth. When changed or mutated, they become oncogenes. They can
then promote tumor formation or growth. Properties of oncogenes include the following:
Mutations in proto-oncogenes are usually acquired. One exception is that mutations
in the RET proto-oncogene can be inherited and cause a condition called multiple endocrine
neoplasia (MEN) type II.
Having a mutation in just one of the two copy pair of a particular proto-oncogene
is usually enough to cause a change in cell growth and the formation of a tumor. For
this reason, oncogenes are said to be dominant at the cellular level.
Tumor promoter genes contribute to development of tumors in general, or to separate
aspects of tumor progression.
Tumor suppressor genes
Tumor suppressor genes are normally present in our cells. When working properly,
they keep the processes of cell growth and cell death (called apoptosis) in check. Through these processes, they can also suppress tumor development. When
a tumor suppressor gene is mutated, this can lead to tumor formation or growth. Properties
of tumor suppressor genes include the following:
Both copies of a specific tumor suppressor gene need to be mutated (both members of
the gene pair) in order to cause a change in cell growth and tumor formation to happen.
For this reason, tumor suppressor genes are said to be recessive at the cellular level.
Mutations in tumor suppressor genes are often acquired. Mutations in both copies of
a tumor suppressor gene pair may happen as the result of aging and/or environmental
A mutation in a tumor suppressor gene can also be inherited. In these cases, a mutation
in one copy of the tumor suppressor gene pair is inherited from a parent. It is present
in all of a person's cells (germline mutation). The mutation in the second copy of
the gene (which is necessary for tumor formation and cell growth change) is acquired
and usually happens only in a single cell or a handful of cells. If the second hit or mutation happens in a type of cell that needs this particular tumor suppressor
gene to control cell growth, the process of tumor formation will begin. This mechanism
is also known as the two-hit hypothesis.
Most of the genes associated with hereditary cancer are tumor suppressor genes. Nonetheless,
most mutations in tumor suppressor genes are not inherited.
DNA repair genes
During cell division, the DNA in a cell makes a copy, or replica, of itself. During
this complex process, mistakes may happen. Mismatch-repair genes code for proteins
that correct these naturally occurring spelling errors in the DNA. When these genes
are altered or mutated, however, mismatches (mistakes) in the DNA remain. If these
mistakes happen in tumor suppressor genes or proto-oncogenes, eventually this will
lead to uncontrolled cell growth and tumor formation. There are other types of DNA
repair genes that repair errors in DNA that happen from mutagenic agents, such as
large doses of radiation. Properties of DNA repair genes include the following:
Mutations in DNA repair genes can be inherited from a parent. They also be acquired
over time as the result of aging and environmental exposures.
DNA repair genes require two mutations (both copies of the gene pair) in order for
the process of tumor formation to happen. For this reason, mismatch-repair genes are
said to be recessive at the cellular level.
Remember that it usually takes mutations in several of these genes for cancer to develop.
In most cases of cancer, all the mutations are acquired. In inherited cancer, one
mutation is passed down from the parent. The remainder are acquired. Because it takes
more than a single mutation to cause cancer, not all people who inherit a mutation
in a tumor suppressor gene, proto-oncogene, or DNA repair gene will develop cancer
within their lifetime.