BRCA1 MUTATION AND RISK OF HEART FAILURE

NEW YORK (Reuters Health) Oct 15 - In addition to promoting breast cancer, mutations in the BRCA1 gene may adversely affect cardiac function and survival, according to the results of an animal study presented Wednesday at the 95th annual Clinical Congress of the American College of Surgeons in Chicago.

"Recent data suggest that carriers of BRCA1/2 mutations exhibit an increase in non-neoplastic death, particularly at older ages," senior researcher Dr. Subodh Verma, from St. Michael's Hospital in Toronto, told Reuters Health. "Our animal model-based data raise the tantalizing possibility that the excess mortality may be due to increased rates of ischemic heart disease as a result of the BRCA1 influence on heart health."

The current data, he added, "provide the first biological clue that individuals who are susceptible to developing breast cancer may also be susceptible to developing heart failure. Additionally, the findings suggest that therapies that increase BRCA1 may represent a new frontier to treat heart failure."

In the new study, Dr. Verma's team found that experimental MI greatly increased BRCA1 expression in mice. Testing in neonatal rat cardiomyocytes showed that overexpression of BRCA1 had a cardioprotective effect, limiting the apoptosis induced by doxorubicin and hydrogen peroxide.

Further study suggested that BRCA1 was achieving these effects, at least in part, by reducing expression of p53.

Given these findings, it is not surprising that a lack of BRCA1 had a harmful effect on cardiac function. BRCA1 knockout mice exposed to doxorubicin had markedly worse cardiac function and survival than did their wild-type counterparts with intact BRCA1.

"The findings represent a paradigm shift in our understanding of BRCA1 as it relates to cancer and may provide the beginning of a new line of investigation linking cancer genes to heart disease," Dr. Verma concluded. "Further clinical studies in BRCA1 mutants may be warranted."