Genes are in the DNA of each cell in your body. They control how the cell functions, including:

• How quickly it grows
• How often it divides
• How long it lives

Researchers estimate that each cell contains 30,000 different genes. Within each cell, genes are located on chromosomes.  

About chromosomes

Chromosomes are the thread-like structures in cells that contain genes. There are 46 chromosomes, arranged in 2 sets of 23.

You inherit one set from your mother and one from your father. One chromosome in each set determines whether you are female or male. The other 22 chromosome pairs determine other physical characteristics. These chromosome pairs are called autosomes.

How genes work

Genes control how your cells work by making proteins. The proteins have specific functions and act as messengers for the cell.

Each gene must have the correct instructions for making its protein. This allows the protein to perform the correct function for the cell.

All cancers begin when one or more genes in a cell mutate. A mutation is a change. It creates an abnormal protein. Or it may prevent a protein’s formation.

An abnormal protein provides different information than a normal protein. This can cause cells to multiply uncontrollably and become cancerous.

About genetic mutations

There are 2 basic types of genetic mutations:

Acquired mutations. These are the most common cause of cancer. They occur from damage to genes in a particular cell during a person’s life. For example, this could be a breast cell or a colon cell, which then goes on to divide many times and form a tumor. A tumor is an abnormal mass. Cancer that occurs because of acquired mutations is called sporadic cancer. Acquired mutations are not found in every cell in the body and they are not passed from parent to child.

Factors that cause these mutations include:

• Tobacco
• Ultraviolet (UV) radiation
• Viruses
• Age

Germline mutations. These are less common. A germline mutation occurs in a sperm cell or egg cell. It passes directly from a parent to a child at the time of conception. As the embryo grows into a baby, the mutation from the initial sperm or egg cell is copied into every cell within the body. Because the mutation affects reproductive cells, it can pass from generation to generation.

Cancer caused by germline mutations is called inherited cancer. It accounts for about 5% to 20% of all cancers.

Mutations and cancer

Mutations happen often. A mutation may be beneficial, harmful, or neutral. This depends where in the gene the change occurs. Typically, the body corrects most mutations.  

A single mutation will likely not cause cancer. Usually, cancer occurs from multiple mutations over a lifetime. That is why cancer occurs more often in older people. They have had more opportunities for mutations to build up.

Types of genes linked to cancer

Many of the genes that contribute to cancer development fall into broad categories:

Tumor suppressor genes. These are protective genes. Normally, they limit cell growth by:

• Monitoring how quickly cells divide into new cells
• Repairing mismatched DNA
• Controlling when a cell dies

When a tumor suppressor gene mutates, cells grow uncontrollably. And they may eventually form a tumor.

Examples of tumor suppressor genes include BRCA1, BRCA2, and p53 or TP53.

Germline mutations in BRCA1 or BRCA2 genes increase a woman’s risk of developing hereditary breast or ovarian cancers and a man’s risk of developing hereditary prostate or breast cancers. They also increase the risk of pancreatic cancer and melanoma in women and men.

Hereditary Cancer Syndromes

Inherited genetic mutations play a major role in about 5 to 10 percent of all cancers. Researchers have associated mutations in specific genes with more than 50 hereditary cancer syndromes, which are disorders that may predispose individuals to developing certain cancers.

Genetic tests for hereditary cancer syndromes can tell whether a person from a family that shows signs of such a syndrome has one of these mutations. These tests can also show whether family members without obvious disease have inherited the same mutation as a family member who carries a cancer-associated mutation.

Many experts recommend that genetic testing for cancer risk be considered when someone has a personal or family history that suggests an inherited cancer risk condition, as long as the test results can be adequately interpreted (that is, they can clearly tell whether a specific genetic change is present or absent) and when the results provide information that will help guide a person’s future medical care.

Cancers that are not caused by inherited genetic mutations can sometimes appear to “run in families.” For example, a shared environment or lifestyle, such as tobacco use, can cause similar cancers to develop among family members. However, certain patterns in a family—such as the types of cancer that develop, other non-cancer conditions that are seen, and the ages at which cancer develops—may suggest the presence of a hereditary cancer syndrome.

Even if a cancer-predisposing mutation is present in a family, not everyone who inherits the mutation will necessarily develop cancer. 

Here are examples of genes that can play a role in hereditary cancer syndromes.

• The most commonly mutated gene in all cancers is TP53, which produces a protein that suppresses the growth of tumors. In addition, germline mutations in this gene can cause Li-Fraumeni syndrome, a rare, inherited disorder that leads to a higher risk of developing certain cancers.
• Inherited mutations in the BRCA1 and BRCA2 genes are associated with hereditary breast and ovarian cancer syndrome, which is a disorder marked by an increased lifetime risk of breast and ovarian cancers in women. Several other cancers have been associated with this syndrome, including pancreatic and prostate cancers, as well as male breast cancer.
• Another gene that produces a protein that suppreses the growth of tumors is PTEN. Mutations in this gene are associated with Cowden syndrome, an inherited disorder that increases the risk of breast, thyroid, endometrial, and other types of cancer.

For more genes that can play a role in hereditary cancer syndromes, see Genetic Testing for Inherited Cancer Susceptibility Syndromes.

Genetic Tests for Hereditary Cancer Syndromes

Genetic tests for mutations that cause hereditary cancer syndromes are usually requested by a person’s doctor or other health care provider. Genetic counseling can help people consider the risks, benefits, and limitations of genetic testing in their particular situations.

A genetic counselor, doctor, or other health care professional trained in genetics can help an individual or family understand their test results and explain the possible implications of test results for other family members.

People considering genetic testing should understand that their results may become known to other people or organizations that have legitimate, legal access to their medical records, such as their insurance company or employer, if their employer provides the patient’s health insurance as a benefit. Legal protections are in place to prevent genetic discrimination, including the Genetic Information Nondiscrimination Act of 2008 and the Privacy Rule of the Health Information Portability and Accountability Act of 1996.

The most commonly mutated gene in people with cancer is p53 or TP53. More than 50% of cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired. Germline p53 mutations are rare, but patients who carry them are at a higher risk of developing many different types of cancer.

Oncogenes. These turn a healthy cell into a cancerous cell. Mutations in these genes are not known to be inherited.

Two common oncogenes are:

• HER2, a specialized protein that controls cancer growth and spread. It is found in some cancer cells. For example, breast and ovarian cancer cells.
• The RAS family of genes, which makes proteins involved in cell communication pathways, cell growth, and cell death.

DNA repair genes. These fix mistakes made when DNA is copied. Many of them function as tumor suppressor genes. BRCA1, BRCA2, and p53 are all DNA repair genes.

If a person has an error in a DNA repair gene, mistakes remain uncorrected. Then, the mistakes become mutations. These mutations may eventually lead to cancer, particularly mutations in tumor suppressor genes or oncogenes.

Mutations in DNA repair genes may be inherited or acquired. Lynch syndrome is an example of the inherited kind. BRCA1, BRCA2, and p53 mutations and their associated syndromes are also inherited.

Challenges in understanding cancer genetics

Researchers have learned a lot about how cancer genes work. But many cancers are not linked with a specific gene. Cancer likely involves multiple gene mutations. Moreover, some evidence suggests that genes interact with their environment. This further complicates our understanding of the role genes play in cancer.

Researchers continue to study how genetic changes affect cancer development. This knowledge has led to improvements in cancer care, including early detection, risk reduction, the use of targeted therapy, and survival.

Further studying cancer genetics may help doctors find better ways to:

• Predict a person’s risk of cancer
• Diagnose cancer
• Treat cancer

Identifying Genetic Changes in Cancer

Lab tests called DNA sequencing tests can “read” DNA. By comparing the sequence of DNA in cancer cells with that in normal cells, such as blood or saliva, scientists can identify genetic changes in cancer cells that may be driving the growth of an individual’s cancer. This information may help doctors sort out which therapies might work best against a particular tumor. For more information, see Tumor DNA Sequencing in Cancer Treatment.

Tumor DNA sequencing can also reveal the presence of inherited mutations. Indeed, in some cases, the genetic testing of tumors has shown that a patient’s cancer could be associated with a hereditary cancer syndrome that the family was not aware of.

As with testing for specific mutations in hereditary cancer syndromes, clinical DNA sequencing has implications that patients need to consider. For example, they may learn incidentally about the presence of inherited mutations that may cause other diseases, in them or in their family members.

@cancerqueries.com