BRCA testing update

[AlaskaAngel]

Getting Better Results from Genetic Testing



Women with strong family histories of breast cancer who receive negative (or normal) genetic tests for BRCA1 and BRCA2 may still be at high risk, according to a study in the Journal of the American Medical Association (March 22). That's because current testing techniques identify only a handful of certain types of the genetic mutations known to cause breast cancer.

Currently in the United States, genetic testing for BRCA1 and BRCA2 is carried out by a single commercial firm, Myriad Genetics Inc., in Salt Lake City. The type of testing that Myriad uses, called sequencing, searches for only five of the most common large rearrangement mutations.

However, over the last several years scientists have discovered many more. To identify them, researchers say, Myriad would have to use a global screening technology, which catches harder-to-spot genetic rearrangements. Because that technology has not yet met clinical standards, Myriad has not used it, says Bill Hockett, executive vice president of communications for the company.

In the JAMA study, researchers looked at 300 breast cancer patients who had strong family histories of breast or ovarian cancer—which would suggest the presence of genetic mutations—but who had normal genetic testing results when sequencing alone was performed. Using multiple screening methods, the researchers found previously unidentified BRCA mutations in 12 percent of the patients.

Later this year Myriad plans to broaden its testing methods in order to detect more of the gene mutations that contribute to breast cancer.

Until then, Mary-Claire King, one of the study's authors, advises women with a strong family history of breast cancer who previously tested negative for the disease to assume that they do have a mutation, but one that science hasn't yet figured out how to identify.

[heblaj01]

If this research is confirmed, the BARD1 gene would account for the 20% of inherited breast cancer cases not associated with the cancers caused by the BRCA1 & BRCA2 genes.
When a BARD1 gene test becomes available, those women at 100% risk will be in position to decide to either monitor more closely symptoms or go to preventative treatment.

http://articles.news.aol.com/news/ar...990003&cid=474
Second Gene Mutation Increases Breast Cancer Risk
By MARILYNN MARCHIONE, AP

(June 19) - Icelandic women with a bad gene that raises their risk of breast cancer were virtually certain to develop the disease if they also had a mutation in a second gene, scientists reported Monday.
It's unknown how much this applies to women in the United States or elsewhere, but researchers believe the discovery will help unravel the genetic underpinnings of the most common cancer in women worldwide.

"How much risk it actually adds is the question. In this (Icelandic) population, it seems to add a significant amount of risk," said Bill Phelps, a genetics expert at the American Cancer Society who had no role in the study.

Two genes discovered a decade ago - BRCA1 and BRCA2 - have been linked to hereditary forms of breast cancer. Women with one of them have 3 to 7 times the risk of developing the disease compared with women who lack such genes.

But they account for only 10 percent to 15 percent of total breast cancer cases, and not even most of the inherited ones, so scientists long have searched for other genes that may act alone or with them to raise risk.

One, called BARD1, now appears to do that.

Researchers led by Dr. Kari Stefansson and colleagues at deCode genetics Inc. in Reykjavik, Iceland, studied 1,090 Icelandic women who had breast cancer and compared them with 703 similar women without the disease.

A specific BARD1 mutation was found in 2.8 percent of women with cancer but only 1.6 percent of women without it.

More surprisingly, the risk of developing breast cancer roughly doubled for women with the BARD1 mutation and the BRCA2 mutation most common in Iceland.

"When you get them together you basically have almost certainty of breast cancer," Stefansson said.

In the United States, BRCA1 is more common than BRCA2, especially among Ashkenazi Jewish women. Many women with one of these bad genes agonize over whether to have mastectomies or other preventive treatments.

"A lot of people don't really want to deal with these issues unless they've had breast cancer" and are worried about it returning, said Ronit Elk, a prevention researcher at the American Cancer Society.

If more research bears out the role of BARD1, women might be able to make better decisions, she said.

The study was published by the online science journal PLoS Medicine. The company conducted and financed the research and said it was working on developing a test for the gene mutation.

The company has long done genetic studies in Iceland because of the availability of a large database on the population.

Breast cancer is the most common major cancer in American women and the second leading cause of cancer deaths in women. About 213,000 new cases are expected to occur in the United States this year and more than 1 million worldwide.

[AlaskaAngel]

Possible locations for breast cancer susceptibility genes identified

Reuters Health
Posting Date: June 21, 2006



Last Updated: 2006-06-21 13:30:30 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A genome-wide linkage search for breast cancer susceptibility genes has helped define possible areas of interest, but has not identified any specific genes, a large international group of researchers report in the June 21st issue of Genes, Chromosomes and Cancer.

Mutations in the known BRCA1 and BRCA2 breast cancer susceptibility genes account for only a minority of the familial aggregation of the disease, Dr. Douglas F. Easton of Cambridge University, UK and colleagues note.

To search for additional susceptibility genes, the researchers studied 149 families that each had at least three members diagnosed with breast cancer before the age of 60 years. At least one of the subjects in each family was tested and found not to carry a BRCA1 or BRCA2 mutation.

The researchers used the logarithm of odds (lods), a method to unify linkage tests, to evaluate the subjects. Lod scores greater than 1 were found in four regions. The maximum lod score of 2.40 was located on chromosome arm 2p in families with four or more cases of breast cancer diagnosed before the age of 50 years.

However, the team adds that the number of linkage peaks did not differ from that expected by chance. The results suggest promising regions for the location of breast cancer susceptibility genes, but "no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2."

Genes Chromosomes Cancer 2006;45:646-655.