Study: Mutations in DNA repair genes and hereditary childhood cancer

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• people with a genetic mutation linked to cancer risk

Relevance: Medium-High

Strength of Science: Medium-High

Research Timeline: Post Approval

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What is this study about?
DNA repair genes help fix damage in cells. When these repair genes do not work properly, cells may grow out of control and lead to cancer.

In many childhood cancers, gene changes occur in the tumor. These changes in cancer cells are not always inherited, or passed down, from a parent.

It is not fully understood how often children inherit changes in DNA repair genes that can lead to their increased risk of developing childhood cancer.

In this study, scientists looked for mutations in 189 DNA repair genes in almost 6,000 children with cancer.

Why is this study important?
Expanding the study of mutations linked to childhood cancers is important because it may lead to the discovery of additional genes that help explain why some childhood cancers develop. Identifying new genes could also lead to improved discoveries in cancer treatment or prevention.

If a childhood cancer survivor learns they have a genetic risk for additional cancers, doctors can give them better advice about checkups, treatments or steps to stay healthy as adults. This information can also help family members understand their own risks and decide if they should get tested, too.

Overall, the study’s findings make it easier for survivors and their families to get information that could protect their long-term health.

Study findings

Scientists looked for inherited mutations in 189 known DNA repair genes in almost 6,000 children with cancer.

They compared their results with more than 14,000 adults who did not have cancer.

Researchers confirmed the importance of mutations in genes known to repair damaged DNA.

*These numbers show how many children in this study had a mutation in the gene. They do not predict an individual child’s risk.

Newly identified gene links

Researchers also found mutations in four DNA repair genes not previously linked to childhood cancer, but may contribute to cancer risk in children.

This study did not estimate the risk for childhood cancers in people with mutations in the genes listed above. Except for TP53, children with inherited mutations in these genes rarely develop cancers.

Family history was available for many of the children studied. For 14 children, there was a family history of cancer.  Some of these familial cancers were associated with the mutated gene found in the child, while others were not. However, based on the available information, a family tree (pedigree) or genetic testing results, researchers could not clearly establish a pattern for when or how a mutation was passed from a parent to a child.

What does this mean for me?

This study confirmed that mutations in certain known DNA repair genes, like mutations in the TP53 gene, are linked to specific childhood cancers. This study also discovered new links between mutations in DNA repair and childhood cancers.

These findings help to increase the understanding of the genetic causes of childhood cancer, especially a type of bone cancer called osteosarcoma. However, further research is needed to confirm these findings, including how much osteosarcoma risk is linked to inherited changes in SMARCAL1.

Overall, the study highlights the importance of understanding how mutations in DNA repair genes contribute to childhood cancer. However, currently it is not recommended that children be tested for genes such as BRCA1, BRCA2 and Lynch syndrome genes linked largely to adult-onset hereditary cancers.

Identifying mutations in children with cancer can help improve early detection and guide genetic testing for families. In the future, genetic testing for inherited mutations in DNA repair genes may also help guide treatment of childhood cancers. However, currently there are no approved indications based on genetic test results to guide treatment of these childhood cancers.

Notably, although inherited mutations in some genes are linked to young-onset cancers, most of the genes found in this study are linked to adult-onset cancers and are not associated with an increased risk for childhood cancer. If you have tested positive for an inherited mutation linked to cancer risk, talk with your doctor or genetic counselor to learn if your gene may be associated with young-onset cancers.

• Has my child had genetic testing for mutations in known cancer-predisposing genes?
  • If my child has an inherited mutation, what should I do about it?
  • Who in my family should also be informed of this result?
  • How do you suggest I share this information with them?
• I had cancer as a child.  Should I have genetic counseling and testing?
• I have an inherited mutation; is it linked to childhood cancer risk? If so, at what age should my child(children) be tested?