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Germline BRCA2 Mutations and Risk of Pediatric or Adolescent Lymphoma

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Key Points

  • Of 1,380 total survivors, researchers identified 13 pathogenic or likely pathogenic BRCA2 mutations in survivors of lymphoma—5 in survivors of Hodgkin lymphoma and 8 in survivors of non-Hodgkin lymphoma.
  • When comparing with controls without cancer, researchers found a statistically significant association between lymphoma and BRCA2 mutations. The association was statistically significant for non-Hodgkin lymphoma but was not considered statistically significant for Hodgkin lymphoma.
  • A genetic counselor obtained cancer-focused family histories for seven of the eight survivors of non-Hodgkin lymphoma with a BRCA2 mutations. Six of the survivors had family histories of cancers considered within the BRCA2-associated cancer spectrum.

A research letter published by Wang et al in JAMA Oncology has found that inherited mutations in the BRCA2 gene are linked to an increased risk for non-Hodgkin lymphoma in children and adolescents.

“The BRCA family of genes are known to be linked to risk for breast and ovarian cancer as well as several other types of adult-onset cancers, but our study shows a relationship between BRCA2 and non-Hodgkin lymphoma diagnosed in childhood,” said corresponding study author Zhaoming Wang, PhD, associate member of the St. Jude Children’s Research Hospital Departments of Epidemiology and Cancer Control and Computational Biology. “This is the second time an inherited BRCA2 mutation has been associated with an increased risk of any primary pediatric or adolescent cancer. BRCA2 recently emerged as an important predisposition gene for childhood-onset medulloblastoma.”

Background and Methods

Survivorship studies have indicated that childhood cancer survivors have a greater risk of secondary cancers later in life than the general public. Additionally, research has shown that when mutations to genes in the BRCA family are inherited, this can put those individuals carrying the mutations at a greater risk of certain cancers. By linking inherited BRCA2 mutations and childhood cancer, this study expands what is known about inherited cancer risk for a new patient population.

This investigation draws on whole-genome sequencing data gathered through the St. Jude Lifetime Cohort study and the Childhood Cancer Survivors Study. Researchers investigated 1,380 lymphoma survivors, which included individuals with both Hodgkin and non-Hodgkin lymphomas.

Findings

Of 1,380 total survivors, researchers identified 13 pathogenic or likely pathogenic BRCA2 mutations in survivors of lymphoma—5 in survivors of Hodgkin lymphoma and 8 in survivors of non-Hodgkin lymphoma. The researchers also observed that members of the cohort who had inherited BRCA2 mutations and were survivors of childhood non-Hodgkin lymphoma were all men.

When comparing with controls without cancer, researchers found a statistically significant association between lymphoma and BRCA2 mutations (OR = 3.3, 95% confidence interval [CI] = 1.7–5.8). The association was statistically significant for non-Hodgkin lymphoma but was not considered statistically significant for Hodgkin lymphoma.

Additionally, a genetic counselor obtained cancer-focused family histories for seven of the eight survivors of non-Hodgkin lymphoma with a BRCA2 mutations. Six of the survivors had family histories of cancers considered within the BRCA2-associated cancer spectrum.

The authors concluded, “The increased non-Hodgkin lymphoma risk observed among BRCA2 mutation carriers supports the inclusion of pediatric or adolescent non-Hodgkin lymphoma in the spectrum of cancers associated with germline BRCA2 mutations. Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non-Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers.”

Disclosure: The research was funded in part by grants from the National Institutes of Health and ALSAC. For full disclosures of the study authors, visit jamanetwork.com.

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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