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Inherited BRCA2 mutations linked to increased risk of childhood lymphoma

July 25, 2019

A report from St. Jude Children's Research Hospital links inherited mutations in the BRCA2 gene with an increased risk of developing non-Hodgkin lymphoma in children and adolescents. The work appears as an advance online publication today in JAMA Oncology.

"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 author Zhaoming Wang, Ph.D., associate member of the St. Jude 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."

This investigation draws on whole genome sequencing data gathered through the St. Jude Lifetime Cohort (SJLIFE) study and the Childhood Cancer Survivors Study. The purpose of these efforts is to learn about the health of adult survivors of childhood cancer and to reduce the late effects of childhood cancer treatments. Wang and his colleagues investigated 1,380 lymphoma survivors, which included individuals with both Hodgkin and non-Hodgkin lymphoma subtypes. The link between inherited BRCA2 mutations was found predominantly with the non-Hodgkin lymphoma subtype.

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.

"The more we know about the biology that drives a particular cancer, the more a patient's care can be precisely tailored," said co-senior author Leslie Robison, Ph.D., chair of the St. Jude Department of Epidemiology and Cancer Control. "This includes cancer prevention and cancer screening, where an understanding of inherited mutations can help us put in place strategies to care for that patient and family long-term."

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. Further research is needed to understand the finding.

"Understanding inherited risk helps childhood cancer survivors and it enables conversations among relatives who can then make decisions about their own health management strategies," said co-senior author Kim Nichols, M.D., director of the St. Jude Cancer Predisposition Division.
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The Cancer Predisposition Program at St. Jude helps evaluate and take care of children who are at increased genetic risk for cancer. The findings in this study have implications for the Cancer Predisposition Program's work, as genetic counselors continue to provide care and guidance to patients and their families.

The genomic data generated through the research described in this paper is freely available to researchers on the St. Jude Cloud platform, a data-sharing resource pioneered by St. Jude and available to the research community worldwide. St. Jude Cloud is one of the world's largest repositories of pediatric genomics data and offers a suite of unique analysis tools and visualizations.

The study's other authors include Carmen Wilson, Gregory Armstrong, Melissa Hudson and Jinghui Zhang, all of St. Jude.

The research was funded in part by grants from the National Institutes of Health (CA021765, CA55727 and CA195547) and ALSAC, the fundraising and awareness organization of St. Jude.

St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food -- because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.

St. Jude Children's Research Hospital

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