Breast cancer

BRCA2 mutations in childhood lymphoma: implications for follow up

Evidence is strengthening for an association between germline BRCA2 mutations and paediatric or adolescent non-Hodgkin lymphoma.

A research letter in JAMA Oncology described the findings of whole genome sequencing in almost 800 five-year survivors of Hodgkin and non-Hodgkin lymphoma.

The study found pathogenic or likely pathogenic BRCA2 mutations in 13 survivors of Hodgkin lymphoma and eight survivors of non-Hodgkin lymphoma.

In comparison to controls without cancer, there was a statistically significant association between lymphoma overall and BRCA2 mutations (OR 3.3).

“When stratified by diagnosis, the association was statistically significant for non–Hodgkin lymphoma (OR, 5.0; 95% CI, 2.1-10.2) but did not achieve statistical significance for Hodgkin lymphoma (OR, 2.1; 95%CI, 0.7-5.1),” the study authors said.

Cancer-focused family histories were available for the seven of the eight non-Hodgkin lymphoma survivors.

“Six survivors had family histories of cancers, including breast, prostate, pancreas and melanoma, all within the BRCA2-associated cancer spectrum.”

A 2018 study from the same research group found BRCA2 was the third most frequently mutated gene among survivors of childhood cancer.

The letter authors, from the St Jude Children’s Research Hospital, Memphis, said genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of paediatric or adolescent non-Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counselled about cancer risk-reducing strategies,” they advised.

Dr James D’Rozario, head of haematology at the Canberra Hospital, told the limbic the findings were very interesting.

“Secondary cancers have invariably been attributed to acquired mutations resulting from DNA damage as a result of the cytotoxics for example, alkylating agents,” he said.

“This introduces a new aspect to it all. It does have implications for testing, particularly where there is a family history of breast cancer, and in survivors of non-Hodgkin lymphoma, which is relatively treatable, they are probably at risk later in life from the more well known BRCA-associated cancers.”

He said non-Hodgkin lymphoma survivors should be followed up with surveillance, counseling and genetic testing where available.

“If you are diagnosed with lymphoma in childhood and have next-gen sequencing that shows up a BRCA2 mutation then you can prepare yourself for the heightened risk.”

Genetic testing was however not currently rebatable and, while it was becoming more widely available, for many people would be out of reach.

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