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The human body is made up of trillions of cells - the basic building blocks of any complex animal.

These cells normally work together to form organs, such as the heart, liver, and skin. In order for cells to work together, they have to have certain traits or characteristics. For example, they need to be able to divide to make new cells at the right time, stay where they’re needed, and not crowd out nearby cells.

Cancer begins when cells in the body become abnormal and start to grow out of control. This is caused by certain changes in a cell’s genes.

What are genes?

Genes are pieces of DNA inside each cell. They tell the cell how to make the proteins it needs to function. Each gene contains the code (instructions) to make a certain protein, and each protein has a specific job. For example, some genes code for proteins that help the cell grow and divide to make new cells. Other genes code for proteins that help keep cell growth under control.

Genes are contained in chromosomes, which are long strands of DNA in each cell. Each chromosome has many different genes.

Most human cells have 23 pairs of chromosomes. One chromosome of each pair is inherited from a person’s mother, and the other comes from their father. This is why children tend to look like their parents, and why they may have a tendency to develop certain diseases that run in their families.

All the cells in the body have the same genes, but each cell uses only the genes it needs. That is, it turns on (activates) the genes it needs at the right time and turns off other genes that it doesn't need. Turning on some genes and turning off others is how a cell becomes specialized, such as becoming a muscle cell or a bone cell, for example. Some genes stay active all the time to make proteins needed for basic cell functions. Other genes are shut down when their job is finished and can be turned on again later if needed.

Changes in genes

While we all have basically the same set of genes, we also have differences in our genes that make each of us unique. 

The ‘code’ or ‘blueprint’ for each gene is contained in chemicals called nucleotides. DNA is made up of 4 nucleotides (A, T, G, and C), which act like the letters of an alphabet. Each gene is made up of a long chain of nucleotides, the order of which tells the cell how to make a specific protein. 

Gene variants and mutations

Some people have changes in the nucleotides of a gene, which are known as variants (or mutations). For example, one nucleotide ‘letter’ might be switched for another, or one or more letters might be missing, when compared to most other people’s genes. 

Gene variants can have different effects on the proteins they code for. For example:

• Some gene variants might not have any noticeable effect on the protein.
• Some variants might lead to very minor changes in the protein. For example, a variant might result in a protein that’s shaped a little differently and is therefore a bit less effective than the ‘normal’ version of the protein.
• Some variants might have larger effects. For example, a variant might result in a protein that doesn’t work at all. 

Gene variants that lead to changes in proteins can affect all of the cells with that variant, which might even affect the whole body.

The overall effects of some? gene variants might not necessarily be ‘good’ or ‘bad.’ For example, gene variants account for differences in people’s hair or eye color. On the other hand, some variants can lead to a disease (such as cancer) or increase the risk of a disease. These are referred to as pathogenic variants. (These are also what many people think of when they hear the term mutation.)

Inherited versus acquired gene mutations

Gene variants, including mutations, can be either inherited or acquired.

An inherited gene mutation, as the name implies, is inherited from a parent, so it’s present in the very first cell (once the egg cell is fertilized by a sperm cell) that eventually becomes a person. Since all the cells in the body came from this first cell, this mutation is in every cell in the body, and can also be passed on to the next generation. This type of mutation is also called a germline mutation (because the cells that develop into eggs and sperm are called germ cells) or a hereditary mutation. 

It typically takes more than one gene mutation for a cell to become a cancer cell. But when someone inherits an abnormal copy of a gene, their cells already start out with one mutation. This makes it easier (and quicker) for other mutations to happen, which can lead to a cell becoming a cancer cell. This is why cancers related to inherited mutations tend to occur earlier in life than cancers of the same type that are not inherited.

Inherited gene mutations are not the main cause of most cancers. To learn about some of the more common inherited gene mutations that can lead to cancer, see Family Cancer Syndromes.

An acquired gene mutation is not inherited from a parent. Instead, it develops at some point during a person's life. Acquired mutations occur in one cell, and then are passed on to any new cells that come from that cell. This mutation cannot be passed on to a person's children, because it doesn’t affect their sperm or egg cells. This type of mutation is also called a sporadic mutation or a somatic mutation.

Acquired mutations can happen for different reasons. Sometimes they happen when a cell’s DNA is damaged, such as after being exposed to radiation or certain chemicals. But often these mutations occur randomly, without having an outside cause. For example, during the complex process when a cell divides to make 2 new cells, the cell must make another copy of all of its DNA, and sometimes mistakes (mutations) occur while this is happening. Every time a cell divides is another chance for gene mutations to occur. The number of mutations in our cells can build up over time, which is why we have a higher risk of cancer as we get older.

Acquired gene mutations are a much more common cause of cancer than inherited mutations.

Other ways gene activity can be changed

Some of the changes inside cells that can lead to cancer don’t involve gene variants or mutations. Cells can turn some of their genes on and off in other ways, and some of these might also affect how a cell grows and divides.

As mentioned earlier, different genes are more active in some cells than in others. Even within a certain cell, some genes are active at some times and inactive at others. Turning these genes on and off isn’t done by changing the DNA sequence (as is the case with variants and mutations). Instead, the changes in gene activity occur by other means known as epigenetic changes. There are several types of these changes:

• DNA methylation: In this type of change, a small chemical group called a methyl group is attached to the DNA so that the gene can’t start the process of making the protein it codes for. This basically turns off the gene. On the other hand, removing the methyl group (in a process called demethylation) can turn a gene on. 
• Histone acetylation/histone modification: Chromosomes are made up of strands of DNA wrapped around proteins called histones. Histone proteins can be changed by adding (or subtracting) a small chemical group called an acetyl group. Adding acetyl groups (acetylation) can activate (turn on) that part of the chromosome, while taking them away (deacetylation) can deactivate it (turn it off). 
  
  Drugs called histone deacetylase (HDAC) inhibitors can help in the treatment of some types of cancer by turning on genes that help control cell growth and division.
• RNA interference: Inside each cell, DNA acts as long-term storage for our genes. But DNA isn’t in the same part of the cell where proteins are made. For a protein to be made, a copy of its genetic code (in the form of messenger RNA, or mRNA), needs to be made from the DNA first. This piece of mRNA can then bring the instructions to the part of the cell where proteins are made. mRNA is only used for a short time to make the protein, and then it’s broken down. If the cell needs more of that protein, it makes more mRNA. 
  
  RNA interference is another way cells can turn off genes. A cell can make other forms of RNA that stick to mRNA. This can cause the mRNA to break down or stop it from delivering its code.
  
  Drugs are being developed to target the forms of RNA involved in RNA interference. This might help turn off specific genes that cause cancer.

How changes in genes can affect cancer risk

Some genes normally help control when our cells grow, divide to make new cells, repair mistakes in DNA, or cause cells to die when they’re supposed to. If these genes aren’t working properly, it can affect cancer risk. For example:

• Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control. 

DNA changes that create oncogenes or that turn off tumor suppressor genes or DNA repair genes might lead to cancer, although typically it takes several gene changes before a cell becomes a cancer cell. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Changes in some other genes don’t lead to cancer directly, but they might still make someone more likely to get cancer. For example, some gene changes can limit how well the body breaks down some of the toxins in tobacco smoke. Among people who smoke, people with these kinds of gene changes might be more likely to get lung and other smoking-related cancers.

Gene changes can also play a role in other conditions that might impact cancer risk. For example, some gene variants can affect body weight. People with extra body weight are more likely to get some types of cancer, so these variants might also indirectly affect cancer risk.

Gene variants and other changes are common. We all have them, and their effects can add up to influence our cancer risk.