Women with mutations in the BRCA1 or BRCA2 genes are well known to have an increased risk of developing both breast and ovarian cancer. As well as this, links have also been shown to both breast and prostate cancer in men and pancreatic cancer in both sexes. Now new research from St Jude's children hospital in Memphis has also linked the presence of mutations in one of the genes; BRCA2 to an increased risk of a type of childhood lymphoma.
"We found that children known as carriers of pathogenic/likely pathogenic BRCA2 mutations will have much higher risk in developing non-Hodgkin lymphoma (NHL)," said Zhaoming Wang, PhD, associate faculty member of the Epidemiology/Cancer Control department at St Jude.
The BRCA genes encode proteins called tumor suppressors, which protect DNA from damage that if unrepaired, can ultimately lead to the development of cancers. Mutations in these genes can make them less effective or completely ineffective meaning that DNA damage can accumulate far more easily in cells, increasing the chance that cancers develop.
The new research could potentially have implications for children of people who are known BRCA2 mutation carriers, but the research is preliminary and the researchers are in the process of figuring out how best to use their results to help people.
"Based on our current study, it is not yet clear that the surveillance for pediatric/adolescent NHL among the mutation carriers would lead to early detection and other medical advantages," said Wang.
However, some experts feel that more research is needed before really concluding that BRCA2 mutations are definitely causing these childhood lymphomas, rather than being more of a coincidence.
"I am not certain I agree with the conclusion. I noted that 6 of the 7 boys in whom the BRCA2 mutation was identified had a formal pedigree drawn by a genetic counselor and had a family history suggestive of a germline BRCA2 mutation irrespective of the childhood lymphoma diagnosis," said Joy Larsen Haidle, genetic counselor at North Memorial Health Cancer Center in Minnesota and the National Society of Genetic Counselor's Cancer Expert.
"Is the BRCA2 mutation causal for the childhood lymphoma, or did the cancer happen by chance in someone who had a family history suggestive of an underlying BRCA2 mutation? While this is an interesting association, the report does not offer strong evidence of causality for the childhood lymphoma and additional research would be ideal," she added.
Responding to the comments, Dr Wang said; "We agree and suggest that additional research is needed in this area. Our data shows that the BRCA2 mutation was present in 1.4% of non-Hodgkin lymphoma survivors, which is five times higher than seen in the general population. The finding of BRCA2 mutations increasing risk for pediatric/adolescent NHL is new to both research and clinical fields. Further study is needed to translate the gene discovery into clinical practice," said Wang.
Hereditary mutations which are known to increase the risk of cancer in children do exist, but are very rare. They include Li Fraumeni syndrome, where tumor suppressor protein p53 is impaired and combined DNA mismatch repair deficiency, where children are born with absent or severely compromised capability of repairing their DNA, leading to a very high chance of them developing cancers in childhood.
However, this new study is only the second time that an increased risk of pediatric cancer has been linked with gene mutations that previously were only thought to cause adult cancers after research last year linked BRCA2 mutations to a type of childhood brain cancer.
"If a mutation is identified, sharing the information among family members is very important to help prevent additional cancers in the family and allow relatives to pursue heightened surveillance. A genetic counselor can help answer questions for family members and facilitate testing if they wish to know if they inherited the risk factor too," said Haidle.
In the meantime, how should families with known BRCA2 mutations interpret this new research?
"Families with BRCA2 mutations may wish to enroll into research to help determine if the association of childhood lymphoma is significant and better define the lifetime cancer estimates. For parents, the study raises questions about childhood risks, but the data is not yet available to provide answers to some of the important questions," said Haidle.
