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Germline BRCA2 Mutation and Risk of Pediatric or Adolescent Lymphoma


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In a study reported in a research letter in JAMA Oncology,1Zhaoming Wang, PhD, and colleagues at St. Jude Children’s Research Hospital, Memphis, found that the presence of a germline BRCA2 mutation increased the risk of development of pediatric or adolescent non-Hodgkin lymphoma.

As noted by the investigators, “In a previous report from the St. Jude Lifetime (SJLIFE) study, BRCA2 (GenBank U43746.1) was the third most frequently mutated gene (14 occurrences) among 3,006 survivors of childhood cancer, with the highest number observed among survivors of lymphoma (7 [1.2%] of 586).”


The increased non–Hodgkin lymphoma risk observed among BRCA2 mutation carriers supports the inclusion of … non-Hodgkin lymphoma in the spectrum of cancers associated with germline BRCA2 mutations.
— Zhaoming Wang, PhD, and colleagues

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The study involved an analysis of whole-genome sequencing data from 1,380 5-year survivors of pediatric or adolescent lymphoma in the SJLIFE study and Childhood Cancer Survivor Study cohorts, including 815 survivors of Hodgkin lymphoma and 565 survivors of non-Hodgkin lymphoma. Among these survivors, 54% were male, the median age at diagnosis was 13.4 years (range = 1.1–22.7 years), and 82% were white.

Associated Risks

A total of 13 pathogenic or likely pathogenic germline mutations in BRCA2 were identified, including 5 in survivors of Hodgkin lymphoma (0.6%) and 8 in survivors of non-Hodgkin lymphoma (1.4%). Mutation carriers did not differ significantly from noncarriers in age at diagnosis (median of 12.8 years old, with a range of 6.0–17.7 years vs median of 13.5 years, with a range of 1.1–22.7 years; P = .40). All eight survivors of non-Hodgkin lymphoma with BRCA2 mutations were male.

A comparison with controls without cancer from the Genome Aggregation Database showed a significant association between all lymphomas and mutations in BRCA2 (odds ratio [OR] = 3.3, 95% confidence interval [CI] = 1.7–5.8). In an analysis stratified by diagnosis, the association was significant for non-Hodgkin lymphoma (OR = 5.0, 95% CI = 2.1–10.2) but not for Hodgkin lymphoma (OR = 2.1, 95% CI = 0.7–5.1).

Research of family histories for seven of the eight survivors of non-Hodgkin lymphoma carrying a BRCA2 mutation showed that six survivors had family histories of cancers in the BRCA2-associated cancer spectrum, including breast, prostate, and pancreatic cancers, as well as melanoma.

The investigators 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.” 

DISCLOSURE: For full disclosures of the study authors, visit jamanetwork.com.

REFERENCE

1. Wang Z, Wilson C, Armstrong GT, et al: Association of germline BRCA2 mutations with the risk of pediatric or adolescent non-Hodgkin lymphoma. JAMA Oncol. July 25, 2019 (early release online).


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