What Causes Thyroid Cancer?

While we know about some risk factors for thyroid cancer, including certain inherited conditions, it’s not always clear exactly what causes thyroid cancer. Here is what we do know about the gene changes (mutations) that contribute to certain types of thyroid cancer.

Gene changes (mutations) and cancer

Cells are the basic building blocks of all living things, including our bodies. Genes are what control how cells function. DNA is the chemical in our cells that makes up those genes. Our DNA, which comes from both our parents, affects more than just how we look.

Cancer is caused by changes in the DNA inside our cells.

Different genes have different functions in our bodies. If they are working properly, certain genes help control when our cells grow, divide to make new cells, or repair mistakes in DNA. They also cause cells to die when they’re supposed to.

If these genes aren’t working properly, it can lead to cells growing out of control. 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.

Any of these types of DNA changes might lead to cells growing out of control and forming a tumor. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Inherited versus acquired gene mutations

People have 2 copies of each gene in their cells. One copy comes from each parent.

Some people inherit DNA changes (mutations) from a parent that increase their risk of thyroid cancer.

But most thyroid cancers are not caused by inherited gene changes. Instead, the gene changes are acquired during a person’s life. Sometimes these changes might be caused by something in a person’s environment, like radiation. But sometimes they may just be random events that happen inside a cell, without having an outside cause.

In different types of thyroid cancer, the cells tend to have changes in different genes.

Doctors sometimes test thyroid biopsy samples for certain gene mutations. This information can help diagnose the cancer. It might also affect a person’s treatment options.

Learn more: Tests for Thyroid Cancer

Papillary thyroid cancer

In about half of all papillary thyroid cancers, the cancer cells have changes in the BRAF gene. This creates a BRAF oncogene that stays turned on all the time, causing the cells to grow out of control.

Less often, the cancer cells have a mutation in one of the RAS genes (creating a RAS oncogene). The RAS genes are closely related to the BRAF gene.

Some papillary thyroid cancers have changes in the RET gene. The altered form of this gene, known as the PTC oncogene, is more common in papillary thyroid cancers in children and in people exposed to radiation. These mutations are usually acquired during a person’s lifetime rather than being inherited, so they are found only in cancer cells and are not passed on to a person’s children.

Changes in other genes can also be seen in papillary thyroid cancer, including those in the NTRK1 and NTRK3 genes.

Follicular thyroid cancer

Follicular thyroid cancers often have changes in one of the RAS oncogenes.

In some follicular cancers, the cells have changes that result in the fusion of the PAX8 and PPAR-γ genes.

Other gene changes are sometimes seen as well, although these are less common.

Anaplastic thyroid cancer

Most anaplastic thyroid cancers are thought to start out as papillary or follicular thyroid cancers, so they often have some of the same mutations described above, such as in the BRAF and RAS genes.

But anaplastic cancers also develop changes in other genes, such as the TP53 tumor suppressor gene, which cause them to grow and spread more quickly.

Medullary thyroid cancer (MTC)

The main gene changes in people with medullary thyroid cancer (MTC) are mutations in different parts of the RET gene. These changes are not the same as the RET gene changes seen in some papillary thyroid cancers (see above).

RET gene changes are found in the cancer cells of about 2 out of 3 people with the sporadic (non-inherited) form of MTC. These gene changes are only in the cancer cells, so they can’t be passed down to a person’s children.

Nearly all people with an inherited form of MTC, such as from multiple endocrine neoplasia type 2 (MEN2), have a mutation in the RET gene. These people inherit the RET mutation from a parent, so it is in every cell in the body and can be passed on to a person’s children.