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DUOX2 Mutation in Familial Thyroid Cancers


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Researchers have identified a new genetic mutation that may cause a type of familial thyroid cancer. According to the researchers, DUOX2 is the first and only mutation associated with familial thyroid cancer to be identified in a gene that is primarily expressed in the thyroid gland. These findings were published by Bann et al in Cancer Research.

People who have a first-degree relative with thyroid cancer have a two- to fivefold increased risk of developing the disease themselves. Identifying DUOX2 has helped the researchers understand why this form of cancer is more inheritable than other cancers.

“Thyroid cancer is common and [it is] on the rise, and hereditary nonmedullary thyroid cancers account for 6% to 10% of cases,” said first author Darrin V. Bann, MD, in a release from the Penn State College of Medicine in Hershey, Pennsylvania. “Prior to this study, there was not much data to explain why this type of cancer was highly heritable.”

Next-Generation Sequencing and Role of DUOX2

The researchers identified a family in which eight people had developed thyroid cancer across four generations. They used next-generation sequencing to examine every gene in the genome for all of the patients with thyroid cancer in the family. When analyzing the data, they discovered all the family members with thyroid cancer had a mutation in a gene called DUOX2—a rare mutation that occurs once in every 138,000 members of the general population.

The DUOX2 gene provides information for the creation of a protein called dual oxidase 2, which produces hydrogen peroxide and is found at high levels in the thyroid gland. After performing a series of biochemical analyses on the protein with the mutation, they were able to determine that the mutated version produced more hydrogen peroxide rather than stopping the production of the chemical. Hydrogen peroxide is used in the final stages of thyroid hormone production, but the researchers believe the excess may cause additional gene mutations, which may increase the risk of thyroid cancer.

“Thyroid cancer is common and [it is] on the rise, and hereditary nonmedullary thyroid cancers account for 6% to 10% of cases. Prior to this study, there was not much data to explain why this type of cancer was highly heritable.”
— Darrin V. Bann, MD

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“Hydrogen peroxide can harm genetic material through a process called oxidative damage,” explained Dr. Bann. “This may be a common theme underlying genetic risk for developing thyroid cancer. If we can identify more mutations that increase risk for oxidative damage, we may be able to develop preventative strategies, including treatments with antioxidants.”

Based on their findings, the researchers decided to see if DUOX2 was related to other genetic mutations associated with nonmedullary thyroid cancers. They found that some individuals with sporadic thyroid cancers had a mutation that increased the amount of DUOX2 in the thyroid gland. These findings suggest to the researchers that dysregulation of hydrogen peroxide may be the cause of other genetic mutations associated with thyroid cancers.

In the future, Dr. Bann hopes knowledge of this mutation can help create new models for studying thyroid cancer in the lab and the development of prevention strategies. While previous mutations have been identified in families with thyroid cancer, Dr. Bann said the DUOX2 mutation is the only one that connects directly to thyroid tissue.

“The individuals with thyroid cancer in the family we studied had a mutation in a gene that is related to thyroid tissue. Finding other families and individuals with this mutation will be essential for confirming our findings,” he concluded.

Disclosure: For full disclosures of the study authors, visit cancerres.aacrjournals.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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