How Genes Cause Cancer
How do genes cause cancer?
To understand the mechanisms of how genes cause cancer, it's important to review some
basic genetic concepts.
Genes are in every human cell. They consist of pieces of DNA (deoxyribonucleic acid)
that tell the cell when to grow and divide. Genes also tell the cell how to make a
precise protein product for a specific job in the body.
Genes come in pairs and work together to make this protein product. One copy of the
gene pair comes from the mother. The other copy comes from the father. Eggs and sperm
are called germ cells. When a change (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.
Mutations that you 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 your children. Most human cancers are thought
to be caused by acquired (somatic) mutations. Germline mutations are involved in a
small portion of cases.
Tumors form when cell growth gets out of control. In the human genome, many types
of genes control cell growth in a very 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 one after another in different
genes in a specific group of cells over time to cause malignancy.
The different types of mutated genes that can lead to 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 things in the environment known to
increase the risk for cancer (carcinogens). The development of mutations is also a
natural part of aging.
These are altered forms of genes known as proto-oncogenes. Proto-oncogenes promote
cell growth. When changed or mutated, they become oncogenes. They can then promote
tumor formation or growth. Properties of oncogenes include:
Mutations in proto-oncogenes are usually acquired.
Having a mutation in just 1 of the 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 (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
Both copies of a specific tumor suppressor gene pair need to be mutated 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, environmental factors,
A mutation in a tumor suppressor gene can also be inherited. In these cases, a mutation
in 1 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 is acquired and usually happens only in a single cell or a handful of cells.
If the second 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 2-hit hypothesis.
Most of the genes linked to hereditary cancer are tumor suppressor genes. But most
mutations in tumor suppressor genes are not inherited.
DNA repair genes
During cell division, the DNA in a cell makes a copy (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
mutated, mismatches (mistakes) in the DNA remain. If these mistakes happen in tumor
suppressor genes or proto-oncogenes, this will lead to uncontrolled cell growth and
tumor formation. Other types of DNA repair genes repair errors in DNA that happen
from mutagenic agents, such as large doses of radiation. Properties of DNA repair
Mutations in DNA repair genes can be inherited from a parent. They can also be acquired
over time as the result of aging and environmental factors.
DNA repair genes need mutations in both copies of the gene pair for the process of
tumor formation to happen. For this reason, mismatch-repair genes are said to be recessive
at the cellular level.
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