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BRCA2 mutation linked to additional cancer types in childhood


BRCA2 mutations already are linked to a number of cancer types, and now researchers have found that it could play a role in the development of childhood lymphomas, as well.

The BRCA2 gene mutation is known to increase cancer risks later in life, but it may also pose a threat in childhood.

Children who inherit the BRCA2 mutation-a mutation on chromosome 13, which normally suppresses cell growth, that could lead to breast, ovarian, prostate, and other cancers later in life-are believed to face an increased risk of developing non-Hodgkin lymphoma in the child and adolescent years, according to a recent report published in JAMA Oncology.

Researchers hypothesized a connection between childhood lymphoma and the BRCA2 gene mutation, and used a cohort of childhood cancer survivors to test the theory. According to the St. Jude Lifetime Cohort (SJLIFE) study, BRCA2 was the third most frequently mutated gene among more than 3000 childhood cancer survivors. The highest prevalence of the gene was noted among survivors of lymphoma, which accounted for 1.2% of the cohort.

Researchers evaluated 1380 children who were 5-year pediatric and adolescent lymphoma survivors-815 of them were survivors of Hodgkin lymphoma and 565 of them were survivors of non-Hodgkin lymphoma. The team used germline whole-genome sequencing with DNA from blood and saliva samples to detect mutations. They found 13 pathogenic or likely pathogenic mutations in BRCA2, with 5 mutations in the Hodgkin lymphoma survivors and 8 mutations in the non-Hodgkin lymphoma survivors. According to the report, researchers also noted that all 8 of the mutation carriers with non-Hodgkin lymphoma were male.

Overall, researchers found a significant association between BRCA2 and non-Hodgkin lymphoma, but the correlation between BRCA2 and Hodgkin lymphoma was not significant.

Zhaoming Wang, PhD, an associate faculty member in the department of epidemiology, cancer control, and computational biology at St. Jude Children’s Research Hospital in Memphis, Tennessee, says the study suggests that pediatric/adolescent non-Hodgkin lymphoma should be included in the list of BRCA2-associated cancers, and screening may eventually be recommended-particularly when there is a family history of BRCA2-associated cancers.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric/adolescent non-Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” Wang says. “At this stage, we’re not sure if surveillance for non-Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantage, which requires further investigations.”

While it’s early yet to make clinical recommendations, Wang says the study is still novel.

“Our report is the first to show the association of BRCA2 mutations with risk of non-Hodgkin lymphoma among pediatric cancer survivors,” Wang says. “Further investigation is needed to evaluate its clinical utility.”

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