January 4, 2012 (Toronto, ON) — Canadian researchers have discovered that the BRCA1 gene is an essential regulator of cardiac function, at least in mice, and may therefore represent a new therapeutic target for heart failure [1].
The findings are also important for cancer patients who have mutations in the BRCA1 and BRCA2 genes — who are at higher risk of breast and ovarian cancer — because it means these individuals could be at increased risk of heart problems as well, say Dr Praphulla C Shukla (St Michael's Hospital, Toronto, ON) and colleagues in their paper published online December 20, 2011 in Nature Communications.
Shukla et al found that mice with BRCA1/2 mutations had much more severe MIs than those without the mutations and a subsequent three to five times higher rate of death, largely due to the development of heart failure.
The results may explain recent observations that BRCA1/2 mutation carriers have an increased risk of nonneoplastic death, particularly in older age, say the researchers.
And they likely have implications for those undergoing chemotherapy too, in that BRCA1 and 2 mutation carriers could be even more susceptible to the cardiotoxic effects of such treatment than average cancer patients, Shukla et al suggest. Mice with the mutations had a twofold increase in heart failure when treated with doxorubicin.
Oncologist and coauthor Dr Christine Brezden-Masley (St Michael's Hospital) says the research is already making her think twice about particular chemotherapy regimens in BRCA mutation carriers.
"When a patient has the mutated gene, I now have to think about how much doxorubicin I'm going to give them or whether we should consider an alternative therapy," she says in a hospital statement [2].
The findings are also important for cancer patients who have mutations in the BRCA1 and BRCA2 genes — who are at higher risk of breast and ovarian cancer — because it means these individuals could be at increased risk of heart problems as well, say Dr Praphulla C Shukla (St Michael's Hospital, Toronto, ON) and colleagues in their paper published online December 20, 2011 in Nature Communications.
Shukla et al found that mice with BRCA1/2 mutations had much more severe MIs than those without the mutations and a subsequent three to five times higher rate of death, largely due to the development of heart failure.
The results may explain recent observations that BRCA1/2 mutation carriers have an increased risk of nonneoplastic death, particularly in older age, say the researchers.
And they likely have implications for those undergoing chemotherapy too, in that BRCA1 and 2 mutation carriers could be even more susceptible to the cardiotoxic effects of such treatment than average cancer patients, Shukla et al suggest. Mice with the mutations had a twofold increase in heart failure when treated with doxorubicin.
Oncologist and coauthor Dr Christine Brezden-Masley (St Michael's Hospital) says the research is already making her think twice about particular chemotherapy regimens in BRCA mutation carriers.
"When a patient has the mutated gene, I now have to think about how much doxorubicin I'm going to give them or whether we should consider an alternative therapy," she says in a hospital statement [2].
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