Clinical Thyroidology® for the Public
Summaries for the Public from recent articles in Clinical Thyroidology
Table of Contents | PDF File for Saving and Printing
THYROID CANCER
From rare exceptions to common findings: implications for managing hereditary thyroid cancer risk
BACKGROUND
Genes code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an individual’s cells and pass genetic traits to offspring. All individuals have 2 sets of genes; 1 set from each parent. When different versions of a particular gene are passed down from each parent, it is termed heterozygous genes and is the most common pairing of genes. If the same version of a particular gene are passed down from each parent, it is termed homozygous.
A small proportion of thyroid cancers are part of rare hereditary (ie. tend to run in families) syndromes caused by distinct gene mutations. For example, medullary thyroid cancer (MTC) can be part of the multiple endocrine neoplasia (MEN) syndrome caused by a RET gene mutation. There are also hereditary syndromes associated with other types of thyroid cancer, such as PTEN hamartoma tumor syndrome (PHTS), familial adenomatous polyposis (FAP) and other rare syndromes, each syndrome being caused by specific gene mutations. At present, thyroid cancer patients do not undergo genetic evaluation unless other relatives are diagnosed with these rare hereditary syndromes.
More recent studies using large databases that include the genetic data of hundreds of thousands of individuals have shown that a considerable proportion of people have genetic mutations associated with thyroid cancer without developing cancer. It has been estimated that only ~53% of individuals who have associated genetic mutations will develop thyroid cancer.
The goal of this study is to evaluate mutations that cause thyroid cancer-associated hereditary syndromes by using two large, public, population-scale databases; the All of Us database from the US and the UK Biobank.
THE FULL ARTICLE TITLE
White SL et al. Population prevalence of the major thyroid cancer–associated syndromes. J Clin Endocrinol Metab. Epub 2025 Apr 15:dgaf236; doi: 10.1210/clinem/ dgaf236. PMID: 40231587.
SUMMARY OF THE STUDY
This study included 245,394 participants from the All of Us research program founded by the US National Institutes of Health. The researchers analyzed genetic data as well as clinical data from electronic health records and self-reported surveys to determine the presence of possible mutations in genes associated with hereditary syndromes and their association with the development of thyroid cancer. The UK Biobank program which included 469,589 participants was used to validate the results from the All of Us program.
The All of Us database included 2,097 patients with a history of thyroid cancer. Overall, 3 genetic syndromes were significantly associated with thyroid cancer in this database: MEN type 2, PHTS, and FAP. A total of 113 individuals carried mutations of the RET gene that causes MEN type 2 syndrome. Mutations in the PTEN gene that causes PHTS were found in 28 individuals, while mutations in the APC gene characteristic for FAP were found in 29 individuals. Comparable results were noted for each syndrome in the UK database. All mutations were heterozygous, meaning that 1 form of the gene had the mutation while the other form of the gene was normal. Most mutations were known as having moderate risk for cancer development. No thyroid cancer patients were found to have mutations in other high-risk genes.
For all 3 syndromes, only a few (less than 20) individuals who carried the mutations known to raise the risk of thyroid cancer were diagnosed with thyroid cancer. The average age of thyroid cancer diagnosis was 56 years for MEN type 2, 28 years for PHTS, and 37 years for FAP. One surprising result was that none of the carriers of the most common MEN2-related mutations, representing 65% of all MEN2 cases in both the US and UK databases, had a thyroid cancer diagnosis in their records.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This large, data-based study showed that genetic mutations characteristic for thyroid cancer-associated syndromes, such as MEN type 2, PTEN hamartoma tumor syndrome, and FAP, are more common than previously estimated. However, this study shows that most people that carry these mutations do not develop thyroid cancer. As genetic testing becomes more common in the general population, causing more individuals to be identified, we need to develop strategies to adequately monitor and treat these individuals, especially to prevent over-treatment.
— Elie Naous, MD and Alina Gavrila, MD, MMSc
ATA RESOURCES
Thyroid Cancer (Papillary and Follicular): https://www.thyroid.org/thyroid-cancer/
Thyroid Cancer (Medullary): https://www.thyroid.org/medullary-thyroid-cancer/
ABBREVIATIONS & DEFINITIONS
Mutation: a permanent change in one of the genes.
Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass genetic traits to offspring.
Heterozygous genes: having different versions of a particular gene from each parent.
Cancer-associated genes: these are genes that are normally expressed in healthy cells. Cancer cells frequently have mutations in these genes. It is unclear whether mutations in these genes cause cancer or are just associated with cancer cells. The cancer-associated genes important in thyroid cancer are BRAF, RET/PTC, TERT and RAS.
Medullary thyroid cancer (MTC): a rare type of thyroid cancer that often runs in families. Medullary cancer arises from the C-cells in the thyroid.
Multiple endocrine neoplasia, type 2A (MEN 2A): A hereditary syndrome caused by RET mutations, in which medullary thyroid cancer is often seen in association with other endocrine tumors such as pheochromocytoma (a tumor of the adrenal glands) and hyperparathyroidism (elevated parathyroid hormone levels caused by tumors of the parathyroid glands).
PTEN Hamartoma Tumor Syndrome (PHTS): A hereditary syndrome caused by PTEN mutations, which is associated with thyroid cancer and other cancers or noncancerous condition.
Familial Adenomatous Polyposis (FAP): A hereditary syndrome caused by APC mutations, which is primarily linked to colon cancer (affected individuals develop many abnormal growths/polyps in the colon, which can transform into cancer if not removed), but also thyroid cancer.
AMERICAN THYROID ASSOCIATION® , ATA® , THYROID® , CLINICAL THYROIDOLOGY® , and the distinctive circular logo are registered in the U.S. Patent and Trademark Office as trademarks of the American Thyroid Association® , Inc.© 2026 American Thyroid Association.
