From: Reuters
Published January 8, 2008 04:10 PM

BRCA genes get help in causing breast cancer: study

By Andrew Stern

CHICAGO (Reuters) - The risk of breast cancer among women carrying the well-known BRCA mutations is also affected by other genes, researchers said on Tuesday.

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.

So 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.

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"The implications of that are that there must be other genetic factors involved here," Dr. Colin Begg of Memorial Sloan-Kettering Cancer Center in New York, who led the study, 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," Begg said.

Begg's team studied 2,000 women diagnosed with breast cancer, and the families of the 181 patients who had BRCA mutations. They found that 5 percent of those with cancer in one breast had a BRCA1 or BRCA2 mutation and 15 percent of those with cancer in both breasts did.

All had been diagnosed early, before the age of 55.

But only 25 percent of all the patients had a close relative with breast cancer.

And 58 percent of those with BRCA1 or BRCA2 mutations had a mother, sister or other close relative with the disease, the researchers said.

They said this means a close relative of a BRCA carrier with breast cancer has a 40 percent risk of developing the disease herself by age 70. But this is an average risk and they found a considerable amount of variation in risk from one family to another.

SEARCH FOR MORE GENES

Among carriers, their risk of developing breast cancer by age 70 has been estimated at anywhere between 50 percent and 85 percent, Begg said.

They looked to see if perhaps the type of BRCA mutation might affect risk, but it did not appear to. Many different types of mutations were found but they usually did not significantly affect whether a woman or her relatives had breast cancer, Begg's team said.

"There's a lot of research going on at the moment in general to find additional breast cancer genes. What we're saying here is that research is likely to be successful," Begg said.

The BRCA1 and BRCA2 mutations are most common among Jews of Ashkenazi decent -- at least 2 percent of these descendants of Eastern European Jews are carriers. The incidence is lower in the general population, but not enough testing has been done to put a firm estimate on it.

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.

(Editing by Maggie Fox and Cynthia Osterman)

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