Study: How many children with cancer have mutations in genes that increase cancer risk?

This article is most relevant for:
Survivors of childhood cancer and people with a family history of relatives diagnosed with childhood cancers

This article is also relevant for:

Checked People with a genetic mutation linked to cancer risk

Checked Previvors

Checked Other mutations: TP53 (Li-Fraumeni)

Checked Special populations: Families with pediatric cancers

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Many genes are associated with increased cancer risk in adults, but it is unclear how common these mutations are in children with cancer. This study found that about 9% of children with cancer carry mutations in a gene that is known to increase cancer risk. Over half of the mutations were in the TP53 gene, which is associated with increased cancer risk at a young age and increased risk of breast cancer in adults. (12/15/2015)


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This study is about:

How often mutations in genes associated with inherited cancer risk occur in children with cancer.

Why is this study important?

Knowing if a child’s cancer is caused by an inherited gene mutation that is associated with increased cancer risk may help doctors and scientists understand the growth of their cancer, expand options to care for the patient, and assure access to genetic counseling for the children’s families.

Study findings: 

  1. About 9% of pediatric cancer patients had an inherited mutation in a gene associated with increased cancer risk.
  2. 40% of children with mutations in genes associated with increased cancer risk had a known family history of cancer.
  3. Most commonly, mutations found were in the TP53 gene, which is associated with increased risk of numerous cancers in children and adults, including breast cancer.

What does this mean for me?

Mutations in genes associated with increased cancer risk in adults are also found in children with cancer. If pediatric cancer occurs in your family, you may want to talk to your doctor about genetic testing.

Questions To Ask Your Health Care Provider

  • As the parent of a child with cancer, should we consider genetic testing?
  • I have a mutation in TP53; what type of screening should my family consider?
  • I carry a mutation in a gene that increases my risk of cancer; what does this mean for my child?
  • I'm an adult survivor of childhood cancer, should I have genetic testing? 


Study background:

While numerous studies have examined the role of inherited mutations that cause adult cancer syndromes, less research has been conducted regarding inherited pediatric cancers. Some pediatric cancers are known to be inherited, yet the genetic basis of many is still unknown. In a paper published in the New England Journal of Medicine, Dr. James Downey and colleagues at the St. Jude Children’s Research Hospital sequenced over 500 different genes, including 65 genes associated with increased cancer risk, in patients who developed cancer before age 20. 

Researchers of this study wanted to know:

How many children with cancer have inherited mutations in a gene that increases cancer risk.

Population(s) looked at in the study:

Researchers tested blood samples from 1,120 cancer patients under 20 years old who had various cancers, including:

  • leukemia (52.5%)
  • brain and spinal cord cancers (21.9%)
  • neuroblastoma (8.9%)
  • bone cancers, including osteosarcoma (3.5%) and Ewing’s sarcoma (4.1%)

Researchers also looked at genetic test results from people without cancer to determine how common mutations in these genes are in the general population. The samples came from: 

  • the 1,000 Genomes Project, a project that provides an overview of human genetic variation
  • the National Database for Autism Research

Study findings: 

  1. About 9% of the pediatric cancer patients had mutations in genes that are already known to increase cancer risk; this is about 9 times higher than what was found in people from the 1,000 Genomes Project (about 1%) and the National Database for Autism Research population (also about 1%).
  2. The most commonly mutated gene—found in 50 of the 95 pediatric cancer patients with mutations—was  TP53. Mutations in this gene cause Li-Fraumeni syndrome, which predisposes people to developing many different types of cancers (including breast, brain and soft tissue cancers), often at a young age.
  3. Other gene mutations associated with increased cancer risk that were found in the pediatric patients included:
    • APC, associated with familial adenomatous polyposis, which is characterized by increased colon cancer risk (6 patients).
    • BRCA2, associated with hereditary breast and ovarian cancer (6 patients).
    • PMS2, associated with Lynch syndrome, which is characterized by increased risk of numerous cancers, including  colon, ovarian, stomach, and brain (4 patients). 
  4. 8 children had mutations in BRCA1 (1), BRCA2 (6), and PALB2 (1), which are associated with adult-onset cancers, including breast cancer. These children had leukemia, central nervous system tumors, neuroblastoma, osteosarcoma, and rhabdomyosarcoma. However, the percentage of children with these mutations was not significantly different from the percentage that has been found in the average population without cancer.
  5. An additional 20% of children had a variant of uncertain significance (VUS) in one of the genes tested, meaning researchers are unsure if the mutation is associated with increased cancer risk.
  6. Only 40% of the patients with these gene mutations and an available family history actually had a family history of cancer in their close blood relatives (parents, siblings, grandparents, aunts, or uncles).


This study did not consider whether or not parents or relatives of the pediatric cancer patients were also mutation carriers; researchers would not be able to tell if some mutations were new or were associated with a cancer risk within the family.

While the researchers found mutations that are known to increased cancer risk, the study did not directly show that the children’s cancers were caused by these mutations. This is particularly important in the case of gene mutations associated with adult-onset cancers, such as BRCA1, BRCA2, and PALB2.  


About 9% of the 1,120 pediatric cancer patients had a mutation in a gene associated with increased cancer risk. This may reflect an underestimate, as the mutations included are already  associated with a hereditary cancer syndrome (such as TP53 for Li-Fraumini syndrome, and BRCA for breast and ovarian cancer) and did not include other genes.

The fact that only 40% of the patients with mutations had a family history indicates that other factors should be involved in determining the need for genetic testing in children with cancer.

It is interesting that 8 of the children had mutations in the BRCA1, BRCA2, or PALB2 genes, which are known predispose adults to cancer. However, this study did not show that the mutations directly led to the cancer in these children. It is important to note that pediatric cancers are still quite rare, and only a very small percentage of patients in this study had mutations in BRCA or PALB2. The results establish no reason to think that mutations in BRCA1, BRCA2, or PALB2 increase risk of pediatric cancers.  

Abnormalities in TP53, a gene that is already known to increase the risk of pediatric cancer, was the most commonly identified mutation in this study. National guidelines for management of people with mutations in TP53 include notifying pediatricians about increased risk of childhood cancers. Also, parents of children in families with known mutations in TP53 are currently offered the option to have their children undergo genetic testing. 

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