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BRCA2 mutation may predispose children to lymphoma
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Inherited heterozygous BRCA2 mutations appeared to increase risk for non-Hodgkin lymphoma in children and adolescents, according to a research letter published in JAMA Oncology.
“The BRCA family of genes is 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,” Zhaoming Wang, PhD, associate member of the departments of epidemiology and cancer control and computational biology at St. Jude Children’s Research Hospital, said in a press release. “This is the second time an inherited BRCA2 mutation has been associated with an increased risk [for] any primary pediatric or adolescent cancer. BRCA2 recently emerged as an important predisposition gene for childhood-onset medulloblastoma.”
Previous data from the St. Jude Lifetime Cohort (SJLIFE) study showed BRCA2 as the third most frequently mutated gene among 3,006 survivors of childhood cancer, with the highest prevalence among survivors of lymphoma (1.2%).
To determine whether BRCA2 is a predisposition gene for pediatric or adolescent lymphoma, Wang and colleagues evaluated 1,380 5-year survivors (median age at diagnosis, 13.4 years; range, 1.1-22.7; 54.2% male) of pediatric or adolescent lymphomas from the SJFLIFE and Childhood Cancer Survivors studies. White patients comprised the majority of both study cohorts (SJLIFE, 81%; Childhood Cancer Survivor Study, 84.1%).
This combined population included 815 survivors of Hodgkin lymphoma and 565 survivors of non-Hodgkin lymphoma.
The researchers conducted germline whole-genome sequencing — using DNA taken from peripheral blood (SJLIFE study) or buccal or saliva samples (Childhood Cancer Survivor Study) — to detect germline single-nucleotide variants and small insertions and deletions.
Results showed 13 pathogenic/likely pathogenic mutations in BRCA2, including five mutations (0.6%) in Hodgkin lymphoma survivors and eight mutations (1.4%) in non-Hodgkin lymphoma survivors.
Mutation carriers and noncarriers appeared comparable in terms of age at diagnosis (median, 12.8 years vs. 13.5 years), and all eight mutation carriers with non-Hodgkin lymphoma were male.
Researchers then compared these data with data from the Genome Aggregation Database, or gnomAD, noncancer cohort. Results showed a statistically significant correlation between lymphoma and BRCA2 (OR = 3.3; 95% CI, 1.7-5.8).
In an analysis stratified by diagnosis, a significant association occurred between BRCA2 and non-Hodgkin lymphoma (OR = 5; 95% CI, 2.1-10.2); however, this correlation did not reach statistical significance for Hodgkin lymphoma (OR = 2.1; 95% CI, 0.7-5.1).
A genetic counselor acquired cancer-specific family histories for seven of the eight survivors of non-Hodgkin lymphoma who carried a pathogenic or likely pathogenic BRCA2 mutation. This revealed family history of cancers among six survivors, including breast, prostate, pancreas and melanoma, all on the continuum of BRCA2-related cancers.
“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,” the researchers wrote. “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.” – by Jennifer Byrne
Disclosure s : The researchers report no relevant financial disclosures.
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