Genetic insights advance understanding of pediatric thyroid cancer

When a child is diagnosed with cancer, parents often want to understand why. For those with pediatric thyroid carcinoma, a rare disease, that question has long gone unanswered. However, a new study is changing that narrative, revealing hidden genetic clues that may help explain why the disease occurs in some children.

Thyroid cancer accounts for roughly 2% to 6% of all pediatric cancers and affects about 700 children in the United States each year. “Over time, we’ve seen a gradual increase — an annual rise of about 1% to 4% in the incidence of thyroid cancer among children. So, for reasons we don’t yet fully understand, more children are being diagnosed today than in the past,” said Kim Nichols, MD, Division of Cancer Predisposition director, St. Jude Department of Oncology. 

Nichols and her team seek to understand whether children with certain cancers carry an underlying genetic predisposition. Genetic predispositions are caused by changes in specific genes that are present in the normal or “healthy” cells of the body and can increase a person’s risk of developing cancer. Identifying these gene changes provides critical insights for treatment planning, cancer surveillance and long-term care. For example, understanding risk enables clinicians to carefully plan screening strategies to detect new cancers at their earliest and most treatable stages. It also helps when considering surgical approaches for treating existing cancers, the choice of anti-cancer medications, and the reduction or avoidance of radiation therapy to prevent specific toxicities. 

Uncovering inherited risks 

To better understand why some children develop thyroid cancer, Nichols and her team conducted a retrospective study of patients treated at St. Jude. They examined genetic testing results to uncover whether predisposing gene changes could help explain the disease’s origins and whether those findings could influence how care is delivered.

“At St. Jude, we are incredibly fortunate to have access to blood samples, tumor samples and genetic data from thousands of children with cancer, which enables our research,” emphasized Nichols. “Over a period of 14 years, we identified 78 pediatric thyroid cancer patients treated at St. Jude. Of those, 71 were seen by our genetic counselors, and their families agreed to participate in genetic testing.”  

The study, published in Clinical Cancer Research, found that 25% of the tested children with thyroid cancer carried pathogenic variants in genes known to increase cancer risk. These included mutations in DICER1, PTEN, APC, RET, RB1 and ELP1, each associated with specific cancer predisposition syndromes. In some cases, these variants may have been inherited, while in others they may have arisen as new mutations during embryonic development.

Additionally, this increased risk varies depending on several factors, including the child’s age at thyroid cancer diagnosis, thyroid cancer histology (the make-up of cells in the tumor) and prior cancer history. Age at diagnosis was one of the strongest predictors of genetic risk. The younger the child at thyroid cancer diagnosis, the more likely they are to carry an inherited predisposition. For example, children diagnosed before age 11 were especially likely to have a genetic cause identified. The findings suggest that every child with thyroid cancer should undergo genetic testing, a significant shift from adult care, where thyroid cancer has less of a genetic basis. 

Combining genetic and clinical insight 

The study drew on the specialized knowledge of genetic counselors. At St. Jude, genetic counselors evaluate a child’s family history and genetic testing results to assess inherited cancer risk, guide families through genetic testing, and provide ongoing education and support based on the results.

“I think we’d really like to better understand the trends we’re seeing in pediatric thyroid cancer,” explained Alise Blake, MS, Department of Oncology, and co-first author of the study. “There has only been one other study like this in children, and with the data we have gathered, my hope is that we can use that information to better understand when and how to screen patients and when is the time to intervene to biopsy or remove the thyroid.”

Genetic counselors are trained primarily in adult oncology, meaning that pediatric cases are often viewed through an adult lens. Currently, adult scoring systems are used to analyze pediatric thyroid ultrasounds, but they do not accurately reflect the differences between children and adults. 

“When it comes to thyroidectomy, we have to decide whether to remove half the thyroid or the whole gland,” said Nichols. “In some cases, clinicians may be performing biopsies a bit too early, though we don’t yet have enough data to say for certain.”

This study is one step closer to developing better pediatric-specific criteria to enhance screening and ensure more accurate assessments of thyroid nodules in young patients.

“We know something must explain why these cancers occur, but right now we are just scratching the surface,” said Nichols. “This study is a small example that sets the stage for much larger investigations in the future.”