What Causes Thyroid Cancer?

Thyroid cancer is linked with a number of inherited conditions (described in Thyroid cancer risk factors), but the exact cause of most thyroid cancers is not yet known.

Certain changes in a person’s DNA can cause thyroid cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look. It also can influence our risk for developing certain diseases, including some kinds of cancer.

Some genes contain instructions for controlling when our cells grow and divide into new cells or when they die.

• Certain genes that help cells grow and divide or make them live longer than they should are called oncogenes.
• Genes that slow down cell division or make cells die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

People get 2 copies of each gene – one from each parent. We can inherit damaged DNA from one or both parents. Most cancers, though, are not caused by inherited gene changes. In these cases, the genes change during a person’s life. They may occur when a cell’s DNA is damaged by something in the environment, like radiation, or they may just be random events that sometime happen inside a cell, without an outside cause.

Papillary thyroid cancer

Several DNA mutations (changes) have been found in papillary thyroid cancer. Many of these cancers have changes in specific parts of the RET gene. The altered form of this gene, known as the PTC oncogene, is found in about 10% to 30% of papillary thyroid cancers overall, and in a larger percentage of these cancers in children and/or linked with radiation exposure. These RET mutations usually are acquired during a person’s lifetime rather than being inherited. They are found only in cancer cells and are not passed on to the person’s children.

Many papillary thyroid cancers have a mutated BRAF gene. The BRAF mutation is less common in thyroid cancers in children and in cancers thought to develop because of exposure to radiation. Cancers with BRAF changes tend to grow and spread to other parts of the body more quickly.

Both BRAF and RET/PTC changes are thought to make cells grow and divide. It is extremely rare for papillary cancers to have changes in both the BRAF and RET/PTC genes. Some doctors now advise testing thyroid biopsy samples for these gene mutations, as they can help diagnose cancer and may also affect the patient’s outlook (see Tests for thyroid cancer).

Changes in other genes have also been linked to papillary thyroid cancer, including those in the NTRK1 gene.

Follicular thyroid cancer

Acquired changes in the RAS oncogene as well as changes in the PAX8–PPAR-γ rearrangement have a role in causing some follicular thyroid cancers.

Anaplastic thyroid cancer

These cancers tend to have some of the mutations described above and often have changes in the TP53 tumor suppressor gene.

Medullary thyroid cancer

People who have medullary thyroid cancer (MTC) have mutations in different parts of the RET gene than people with papillary carcinoma. Nearly all patients with the inherited form of MTC and about 1 of every 10 with the sporadic (non-inherited) form of MTC have a mutation in the RET gene. Most patients with sporadic MTC have gene mutations only in their cancer cells. People with familial MTC and MEN 2 inherit the RET mutation from a parent. These mutations are in every cell in the body and can be detected by DNA tests.