Genes have plans for how cells should work and grow. Cancer is caused by a change or mutation of genes. The changes may be caused by things in the world around us or by flaws in natural process. Here are different types of genetic changes which may lead to cancer and examples of what may cause them.
Genes are held in DNA. DNA has millions of chemical building blocks called bases. The bases are instructions for how the cells works. A gene is a specific combination of bases. One gene code can have instructions to build one protein.
Image 1: Structure of DNA
Mutations are changes in parts that make up a gene. It may occur in one of several ways:
- The simplest is a change in a single base that makes up a gene.
- Bases may be added or deleted when it shouldn't.
- Large segments of DNA are accidentally repeated, deleted, or moved.
The mutated genes change how certain proteins are made. The proteins may turn other genes on or off. This can change how the cells work and reproduce and lead to cancer cell behavior such as uncontrolled growth and lack of contact inhibition. Contact inhibition is a natural shut off switch for cell reproduction when other cells are near. It stops overgrowth of cells. Changes in genes may also affect how the cell reacts to chemo- or radiation therapy.
There are two main types of genetic changes:
- Hereditary mutations
- Acquired mutations
Hereditary mutations are passed through families, from parent to child before birth. The changes can be found in nearly all the cells of the body. A genetic mutation does not guarantee that cancer will develop. It does increase the risk of cancer, in some cases by a large amount. Only a small amount of cancers are caused by inherited mutations. For example, BRCA1 and BRCA2 are fairly well known genetic changes related to breast cancer. However, these changes are linked to less than 10% of all breast cancers.
Acquired mutations happen at some point in a person’s lifetime. It may be caused by exposure to things around them like tobacco, radiation, or toxic chemicals or result of the aging process. These mutations are not passed through family genetics.
Mutagenesis is the process of change to a gene. It may be caused by a spontaneous error that happens in natural process or agent such as cigarette smoking or radiation.
There are 3 types of genes that are most often involved:
- Tumor suppressor genes
- DNA repair genes
Certain genes control cell growth. Abnormal forms of these genes are called oncogenes. They instruct cells to make proteins that cause excessive cell growth and division.
Example 1: a gene called the ras gene makes the ras protein. The ras protein tells cells when to divide. The ras gene is often inactive in healthy genes. A mutation in the ras gene will activates the ras protein. The cells will be signaled to divide even when they should not. The ras gene is mutated in about 25% of all cancers.
Example 2: oncogenes also alter enzymes called protein kinases. They help to control many actions of the cells, such as cell division. Oncogenes may alter the enzymes or cause the cells to make too much. It can cause continuous cell division even if it is not needed. Many cancers, such as bladder cancer, breast cancer, and chronic myeloid leukemia (CML) have these altered enzymes. Image 2 illustrates the differences between normal genes and oncogenes.
Image 2: Oncogenes
Tumor Suppressor Genes
Tumor suppressor genes make proteins that slow or stop cell growth and division. The proteins help keep growth and division in check. They can also stop damaged cells from reproducing. Change in these genes may lead to missing or damaged proteins. The loss of such proteins allow a cell to grow and divide in an uncontrolled way. Image 3 illustrates the differences between normal genes and tumor suppressor genes.
Image 3: Differences between tumor suppressor genes and normal genes
One protein made through the tumor suppressor gene is called p53. The p53 protein stops growth and division in cells that have DNA damage. The protein stops cells from growing or dividing into new cells. This will lead to the cell dying off without passing the damaged DNA to other cells during cell division. A mutated p53 gene will allow cells with damaged DNA to survive and divide. The damaged DNA can then be passed on to the cells created during cell division. Each new copy of damaged DNA increases the risk of developing cancer. The p53 gene is defective in most cancers.
DNA Repair Genes
DNA repair genes make proteins that can fix problems in DNA. There are millions of DNA codes that are replicating all the time in the body, so mistakes can happen. These proteins can repair mistakes so that the cell can work normally and the new cells will not have damaged DNA. Damage to the DNA repair gene may stop this from happening. The more damaged DNA there is, the higher the risk of cancer. For example, a defect in repair genes can cause xeroderma pigmentosum. It is a problem repairing DNA in skin cells after sun exposure. People with this condition have much higher rates of skin cancer. Some types of hereditary colon cancer are also linked to defects in DNA repair. Image 4 illustrates the effects of DNA repair genes.
Image 4: DNA Repair Genes
There is often more than one mutation present with cancer. Most cancers are likely the result of a combination of mutations above. This theory believes cancer cells are only created when the tumor suppressor genes are shut off just as the oncogenes are turned on and the repair genes are shut off.
Cancer cells are more likley to get genetic defects as they rapidly divide. Each defect can lead to more mutations. An enormous number of genetic mutations may happen by the time it take a single cancer cell to develop into a tumor (about a billion cells). Image 5 illustrates how multiple mutations may eventually lead to cancerous tumor.
Image 5: Tumor Suppressor Genes and cell growth and division
Cellular and molecular basis of cancer. Merck Manual Professional Version website. Available at: http://www.merckmanuals.com/professional/hematology-and-oncology/overview-of-cancer/cellular-and-molecular-basis-of-cancer. Accessed January 29, 2021.
What is cancer? American Cancer Society website. Available at: http://www.cancer.org/cancer/cancerbasics/what-is-cancer. Accessed January 29, 2021.
What is cancer? National Cancer Institute website. Available at: http://www.cancer.gov/cancertopics/what-is-cancer. Accessed January 29, 2021.
Last reviewed January 2021 by EBSCO Medical Review Board Last Updated: 1/29/2021