updated 11/20/2006 3:46:51 PM ET 2006-11-20T20:46:51

Women with close relatives suffering from breast cancer who do not have the main genetic mutations linked to the illness still have a higher than average risk of developing the disease, doctors said on Tuesday.

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Even if they test negative for the BRCA1 and BRCA2 faults, they are three times more likely to be diagnosed with breast cancer by the age of 50 than other women.

“Despite the fact they have not inherited the BRCA 1 or BRCA2 faults, they have a risk of inheriting other genetic faults, many of the genes of which we have not identified,” said Professor Gareth Evans, of St Mary’s Hospital in Manchester, England.

“Their chances of developing breast cancer under 50 were three times that in the general population,” he told Reuters.

Although the raised risk is relatively small, a rise from 2 percent to 6.4 percent, Evans suggested women in families with a history of breast cancer should be given extra screening for the disease at a younger age -- probably starting at 35 years old.

Genetic mutations account for about five percent of breast cancer cases in developed countries. Although changes in the BRCA1 and BRCA2 genes are the leading known causes, scientists suspect there are many more genes involved.

“We now know there may be 40 or 50 genes that increase breast cancer risk,” Evans said. “We are only dealing with the two that are the tip of the iceberg but underneath there is a whole raft of other genetic faults that may only slightly increase your risk.”

He and his team tested for genetic faults in 531 close relatives, mainly sisters and daughters, of 277 women with breast, ovarian or both cancers.

About half of the women had negative results for the BRCA1 and BRCA2 faults, including 28 who developed breast cancer and four who were diagnosed with ovarian cancer.

Evans and his team found four different BRCA1 and BRCA2 phenocopies in women who tested negative for the mutations. A phenocopy occurs when a patient tests negative for the genetic fault but develops the condition to which it predisposes them.

The researchers, who reported the findings in the Journal of Medical Genetics, said the phenocopy is probably due to other alterations, or modifier genes, that mimic the changes produced by the specific genetic fault.

“It is clear it is not the simple story of you either carry a high-risk gene or you don’t. It is a spectrum of risks due to a whole host of genetic factors,” said Evans.

“Even when you are in a high-risk family with BRCA1 and BRCA2, you still have to take into account these other genetic factors that may be in those families,” he added.

Breast cancer is the most common cancer in women, with more than a million cases detected worldwide each year, according to the International Agency for Research on Cancer (IARC) in Lyon, France.

Copyright 2012 Thomson Reuters. Click for restrictions.


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