Researchers at 20 institutions in the US and Europe analyzed the complete sequence of the BRCA1 gene, a gene known to be associated with increased risk of breast and ovarian cancer, in 798 women. The women were already believed to be at increased risk because of  factors including multiple cases of breast cancer, early age of breast cancer diagnosis or cases of ovarian cancer.

The researchers found that 102 women, or 12.8%, had harmful mutations of the BRCA1 gene; 50 had new genetic alterations that included 24 harmful mutations; 24 were variants of unknown significance; and two were rare polymorphisms. This large study confirmed that certain factors appear to determine a woman's chances of carrying a harmful mutation of BRCA1: specific diagnoses (unilateral or bilateral breast cancer with or without ovarian cancer); early age of diagnosis; ethnicity and family history of cancer.

Some ethnic groups appear to be at increased risk for the BRCA mutations. Some two percent of the three million U.S. Jewish women of Ashkenazi descent carry BRCA1 mutations. Of the 71 Ashkenazi Jewish women in the sample, 24 had harmful BRCA1 mutations.

"This study may serve as a reference tool for physicians and genetic counselors to determine patient risk of having a BRCA1 mutation, which causes increased risk of breast and ovarian cancers. Family history, age of onset and ethnicity are all essential ingredients to the cancer puzzle. This study will assist physicians in determining which patients are at highest risk of having a BRCA1 mutation and will help those women and their family members to seek care that may save their lives," said Donna Shattuck-Eidens, Ph.D., of Myriad Genetics, Inc., Salt Lake City, Utah.

Previous studies have shown that five percent to 10 percent of female breast cancer is due to inheritance of an altered, or mutated, copy of one of two genes known as BRCA1 and BRCA2. Research has also shown that women who inherit a mutated copy of the BRCA1 gene have an elevated lifetime risk of breast cancer of up to 87 percent by the age of 70, compared with only 10 percent for the rest of the population.

There are implications for family members of persons carrying a mutation, say the researchers: "Relatives of cancer patients with BRCA1 or BRCA2 mutations are at risk for early-onset breast-ovarian cancer. Once a mutation is identified in a case using full sequence analysis, family members can be tested for only that mutation. People who test negative for this mutation-specific test do not carry the mutation and are at no increased risk by being related to carriers and have no risk of passing the mutation to their offspring. If there is no evidence for a breast-ovarian cancer gene inherited from the other side of the family, they can be considered to have breast-ovarian cancer risk equal to that of the general public."

In the United States, a woman's lifetime risk of breast cancer is 10 percent by the age of 70 years, with more than 180,000 new cases of invasive breast cancer being diagnosed and more than 43,000 women dying from this disease annually. Breast cancer etiology is multifactorial, involving environmental factors, hormones, genetic susceptibility and genetic changes during progression.

The research appear in the October 15, 1997  issue of The Journal of the American Medical Association (JAMA)