Genes and Cancer

Overview

Genes are the instructions in our DNA that control how cells grow, divide and work. Changes in genes can upset normal cell behavior and raise the risk of cancer.

What Genes Are

A gene is a small piece of DNA that tells a cell how to make something it needs. Most genes hold the code for one protein, and each protein has its own job — some help cells grow and divide, others control how fast they grow. Genes sit on chromosomes, long strands of DNA in the nucleus (the control center) of each cell. Most human cells have 23 pairs of chromosomes, one of each pair from each parent. That is why children often look like their parents, and why some diseases run in families.

Every cell has the same genes but uses only the ones it needs, turning genes on and off at the right times. This is called gene expression, and it is how a cell becomes, for example, a muscle cell or a bone cell. Some genes stay on all the time for basic cell work; others switch on and off as needed.

Gene Changes

DNA is built from four building blocks called nucleotides: adenine (A), thymine (T), guanine (G) and cytosine (C). Their order in a gene tells the cell how to make a protein, the way letters spell words. A gene change, or mutation, is a change in that order — a letter changed, missing or added. Some changes have no effect, some make a protein work less well, and some stop it working at all. Many changes only explain normal differences such as hair or eye color. Changes that cause disease or raise disease risk, such as cancer risk, are called pathogenic.

Gene changes happen often, and the body fixes most of them. One change alone probably will not cause cancer. Cancer becomes more likely as changes build up over many years, which is why cancer is more common in older people.

How Gene Changes Affect Cancer Risk

Three kinds of genes matter most. Oncogenes are overactive versions of genes that normally help cells grow, divide or survive; they can make cells grow out of control. Tumor suppressor genes normally slow cell division or make damaged cells die; when they are turned off, cells can grow out of control. DNA repair genes fix mistakes in DNA; when they stop working, errors build up. It usually takes several gene changes to turn a cell into a cancer cell.

Other gene changes raise risk indirectly. Some make it harder for the body to break down toxins in tobacco smoke, raising the risk of lung cancer and other smoking-related cancers. Some affect body weight, and excess body weight is linked to a higher risk of some cancers.

Inherited and Acquired Changes

An inherited (germline or hereditary) change comes from a parent. It is in the first cell formed when egg and sperm join, so it is in every cell of the body and can be passed to children. Because it gives cancer a head start, cancers linked to inherited changes often appear at a younger age. Still, only about 5% to 10% of cancers are caused by inherited changes.

An acquired (somatic) change happens during life. It starts in one cell and passes to the cells that come from it. It cannot be passed to children, because it does not affect egg or sperm cells. Most cancers come from acquired changes. They can be caused by DNA damage, for example from radiation or some chemicals, or happen by chance when a cell copies its DNA to divide. Each division is another chance for a mistake, which is one reason cancer risk rises with age.

Epigenetic Changes

Cells can also turn genes on or off without changing the DNA sequence. These are called epigenetic changes, and they are an important area of cancer research and treatment:

• DNA methylation — a small chemical (a methyl group) attaches to DNA and turns a gene off; removing it (demethylation) can turn the gene back on.
• Histone modification — DNA is wrapped around proteins called histones. Adding acetyl groups (acetylation) can turn genes on; removing them (deacetylation) can turn genes off. Medicines called histone deacetylase (HDAC) inhibitors treat some cancers by turning on genes that help control cell growth.
• RNA interference — cells copy a gene into messenger RNA (mRNA) to make a protein. Other RNA molecules can stick to the mRNA and destroy or block it, so the gene does not work. Medicines are being developed that use this to turn off cancer-causing genes.

Questions to Ask Your Doctor

• Based on my family history, could I have an inherited gene change that raises my cancer risk?
• Should I see a genetic counselor or have genetic testing?
• Was my cancer more likely caused by inherited or acquired gene changes?
• If I have an inherited gene change, what does it mean for my children and other relatives?
• Are there treatments that target the gene changes in my cancer?

Learn More

See Oncogenes, Tumor Suppressor Genes and DNA Repair Genes and Genomic and Genetic Testing for Cancer, and the Precision Medicine group under Cancer Treatments.

Source: https://www.cancer.org/cancer/understanding-cancer/genes-and-cancer.html