In addition to putting carriers at increased risk for breast and ovarian cancers, BRCA2 germline mutations carriers are also at increased risk for pediatric and adolescent non-Hodgkin lymphoma (NHL), according to data from the SJLIFE study.
Prior data from the study showed that BRCA2 was the third most frequently mutated gene among 3006 survivors of childhood cancers, with the highest incidence among survivors of lymphoma. To investigate this connection further, researchers conducted whole-genome sequencing on 1380 5-year survivors of pediatric or adolescent lymphomas. Median age at diagnosis was 13.4 years.
Among these survivors, 12 pathogenic or likely pathogenic BRCA2 mutations were identified, a rate of 0.6% among Hodgkin lymphoma survivors and 1.4% among NHL survivors. All 8 survivors of NHL with a BRCA2 mutation were male.
Compared with a group of controls without cancer, survivors with BRCA2 mutations were at more than 3 times the risk for lymphoma (odds ratio, 3.3; 95% CI, 1.7-5.8). When looked at by specific diagnosis, only the association between the aberration and NHL was statistically significant (OR, 5.0; 95% CI, 2.1-10.2).
When family histories were obtained for 7 of the 8 NHL survivors with BRCA2 mutations, 6 were found to have family histories of breast, prostate, and pancreatic cancers, as well as melanoma.
“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,” the researchers wrote. “Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies.”
Wang Z, Wilson CL, Armstrong GT, et al. Association of germline BRCA2 mutations with the risk of pediatric of adolescent non-Hodgkin lymphoma [published online July 25, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.2203