Toronto researchers have discovered evidence that a genetic mutation linked to higher rates of breast cancer may also play a critical role in regulating proper heart function.
The findings could have major significance for people with that genetic mutation. But they could also lead to new ways of treating all patients with heart disease.
“I do believe that we’re at the beginning of a completely new way of looking at how the breast cancer gene may be a marker of an increased risk of cardiovascular disease,” said Subodh Verma, a cardiac surgeon at St. Michael’s Hospital.
In a new study published in the journal Nature Communications, researchers describe how they manipulated a specific gene in mice to determine the impact on the heart.
The BRCA1 gene is known as a tumour suppressor and produces a protein that helps repair damaged DNA. People who have variants, or mutations, of this gene, have a higher risk of developing breast cancer, as well as cervical, uterine, pancreatic and other types of the disease. Researchers believe this is because the mutation prevents important DNA repair from occurring, which could allow cells to grow uncontrollably and form a tumour.
Certain populations, such as those with a family history of multiple cases of breast cancer, cases of both breast and ovarian cancer, or those of Ashkenazi Jewish descent, are more likely to have the mutation.
Dr. Verma wanted to see whether the genetic mutation causing problems with DNA repair had health implications beyond cancer.
To test the theory, Dr. Verma and colleagues deleted the BRCA1 gene from the hearts of mice and then induced heart attacks in them.
The researchers found that mice without the BRCA1 gene had twice as serious heart attacks and a much higher risk of dying than other mice. They also noted that mice without the BRCA1 gene in the heart were more likely to develop heart failure following a heart attack.
“It’s a hugely important and surprising observation that [BRCA1]is also a critical gatekeeper of heart health,” Dr. Verma said.
It means women carrying mutated forms of BRCA1 may have a previously unrecognized risk of developing heart disease.
If true, this could have implications for the type of cancer treatment patients with the genetic mutation receive, as many types of chemotherapy drugs are known to be linked to an increased risk of heart problems. A woman with a BRCA1 mutation may be particularly vulnerable to those negative heart effects.
To test this theory, Dr. Verma deleted the BRCA1 gene from hearts of mice and gave them doxorubicin, a standard chemotherapy drug for many types of breast cancer. Those mice receiving the drug suffered significantly higher rates of heart failure than those not taking it.
“Maybe we have to be a bit more careful about how much chemotherapy we give [patients with the BRCA1 mutation]and at what dose,” Dr. Verma said.
But Steven Narod, senior scientist at Women’s College Research Institute in Toronto, said it’s still too early to draw real conclusions from the study. While interesting, he said much more work needs to be done before these findings should be used as a basis for altering treatment for breast cancer.
Dr. Narod added that the hospital has treated about 5,000 women with the BRCA1 mutation who had breast cancer. Of those, just under 700 have died and of those, only four succumbed to heart disease. It’s possible that more cases of heart disease will show up in this population as they age, but it’s too soon to tell what role the BRCA1 gene plays in human cases of heart disease.
The study also raises questions about whether men carrying the BRCA1 mutation also face an increased risk of developing heart disease, Dr. Narod said.
Dr. Narod cautioned that this new research needs to go a long way before its true significance can be known.Report Typo/Error