All cancer cells occur because of gene mutations. A mutation is a change or error that occurs in the deoxyribonucleic acid (DNA; the complex set of instructions that tells every cell in a person's body how to function). Genes are the basic biologic units passed from parent to child that provide information about a person's physical characteristics, such as eye color or risk of getting a certain disease. Genes are located on chromosomes (strands of DNA).

Each cell in a person's body contains about 20,000 to 25,000 genes. They are located on 46 chromosomes, which are arranged in two sets of 23 chromosomes—one set inherited from the mother and one set inherited from the father. One chromosome in each set of 23 determines whether a person is female or male (these are called the X and Y chromosomes). The other 22 chromosome pairs, called autosomes, determine other physical characteristics.

About genetic mutations

There are two basic types of genetic mutations: germline and acquired. If the mutation is passed directly from a parent to a child, it is called a germline mutation. This means that the mutation is present in every cell of an individual's body, including the reproductive sperm cells (in a boy's body) and egg cells (in a girl's body). Because the mutation affects reproductive cells, it is passed from generation to generation. Cancer caused by germline mutations is called inherited cancer, which accounts for 5% to 10% of all cancer cases.

Acquired mutations occur during a person's life, and they are not passed from parent to child. Factors such as tobacco, ultraviolet (UV) radiation, viruses, and age cause these mutations. Cancer that occurs because of acquired mutations is called sporadic cancer and is much more common than familial cancer.

Mutations and cancer

Mutations happen often, and the human body has processes in place to correct most of these changes. Depending on where in the gene the change occurs, a mutation may be beneficial, harmful, or make no difference at all. Therefore, the likelihood of one mutation leading to cancer is small. Usually, it takes multiple mutations over a lifetime to cause cancer. This is why cancer occurs more often in older people, for whom there have been more opportunities for mutations to build up.

Types of genes linked to cancer

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

• Tumor suppressor genes are protective genes. Normally, they suppress (limit) cell growth by monitoring the rate at which cells divide into new cells, repairing mismatched DNA (a cause of mutations), and controlling cell death. When a tumor suppressor gene is mutated (due to heredity or environmental factors), cells grow uncontrollably and may eventually form a mass called a tumor. BRCA1, BRCA2, and p53 are examples of tumor suppressor genes. Germline mutations in BRCA1 or BRCA2 genes increase a woman's risk of developing hereditary breast or ovarian cancers [2]. The most commonly mutated gene in people who have cancer is p53. In fact, more than 50% of all cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired mutations. Germline p53 mutations are exceptionally rare.
• Oncogenes turn a healthy cell into a cancerous one. HER2 (a specialized protein that controls cancer growth and spread, found on some cancer cells, such as breast and ovarian cancer cells) and the ras family of genes (genes that make proteins involved in cell communication pathways, cell growth, and cell death) are common oncogenes. Mutations in these genes are acquired (not germline or inherited).
• DNA repair genes fix mistakes made when DNA is replicated (copied). If a person has a mutation in a DNA repair gene, these mistakes are not corrected. Mistakes that aren't fixed become mutations, which may eventually lead to cancer (especially if the mutation occurs in a tumor suppressor gene or oncogene). Mutations in DNA repair genes can be inherited in the germline (in Lynch syndrome [3], for example) or acquired.

Despite all we know about the different ways cancer genes work, many cancers cannot be tied to a specific gene. It is likely that multiple different genes are involved in the development of cancer. Learn more about cancer risk [4].

In the future, doctors hope to learn more about the role of genetic changes in the development of cancer, which may lead to improved cancer treatment and prevention strategies.

More Information

Genetics [5]

Explaining Cancer Genome Research [6]

Facts About Personalized Cancer Medicine [7]

Additional Resources

National Cancer Institute: Cancer Genetics [8]

Last Updated: March 26, 2012