The risk of breast cancer among women carrying the well-known BRCA mutations is also affected by other genes, researchers said yesterday.
The study of close relatives of breast-cancer patients who had one of the BRCA mutations showed the risk of the disease varied greatly between families, indicating that other genes must be involved.
A woman who knows she has a BRCA1 or BRCA2 mutation still cannot know precisely what her risk of breast cancer is, the researchers reported in the Journal of the American Medical Association.
"The implications of that are that there must be other genetic factors involved here," study leader Colin Begg of Memorial Sloan-Kettering Cancer Center in New York said in a telephone interview.
"Because if some carrier families have higher risks than other carrier families, presumably there are other genes being passed through these families that elevate or lower the risks," Dr. Begg said.
His team studied 2,000 women diagnosed with breast cancer, and the families of the 181 patients who had BRCA mutations. They found that 5 per cent of those with cancer in one breast had a BRCA1 or BRCA2 mutation and 15 per cent of those with cancer in both breasts did.
All had been diagnosed early, before the age of 55.
But only 25 per cent of all the patients had a close relative with breast cancer.
Among those with BRCA1 or BRCA2 mutations, 58 per cent had a mother, sister or other close relative with the disease, the researchers said.
This means that a close relative of a BRCA carrier with breast cancer has a 40-per-cent risk of developing the disease herself by the age of 70, they said. But this is an average risk, and there is a considerable amount of variation in risk from one family to another.
Among carriers, their risk of developing breast cancer by age 70 has been estimated at anywhere between 50 per cent and 85 per cent, Dr. Begg said.
They looked to see if perhaps the type of BRCA mutation might affect risk, but it did not appear to. Many different mutations were found, but they usually did not affect whether a woman or her relatives had breast cancer, the team said.
"There's a lot of research going on at the moment in general to find additional breast-cancer genes," Dr. Begg said. "What we're saying here is that research is likely to be successful."
About 465,000 women died of breast cancer last year, making it the leading cause of cancer death among women worldwide, according to the World Health Organization.
