Scientists Speedily Locate a Gene That Causes Breast Cancer; BetterScreening Is Seen
By GINA KOLATA
Published: December 21, 1995
With record speed, scientists have found a new gene that, when mutated, causes breast cancer. Together with a different breast cancer gene, isolated 14 months ago, the two genes account for at least 80 percent of the breast cancer that occurs in women with strong family histories of the disease.
Scientists say that the discovery means they will be able to offer greatly improved genetic screening to women in so-called breast cancer families. And, they said, they hope to use the gene to understand why breast cancer, of all sorts, occurs in the first place.
Familial breast cancer accounts for only 5 percent of the 185,000 women who are found to have breast cancer each year, according to the American Cancer Society, but that amounts to 9,250 cases.
"For women, I think it means a better test will be available," said Dr. Barbara Weber, who is director of the breast cancer center at the University of Pennsylvania Medical Center. Women with strong family histories of breast cancer already had the option of being tested for mutations in the gene found last year, called BRCA1, but changes in that gene accounted for only about half of inherited breast cancer.
Mutations in BRCA2 are thought to account for at least an additional third of hereditary breast cancer and possibly all of it that is not caused by BRCA1 mutations. Women who inherit a single copy of either mutated gene have an 80 percent chance of developing breast cancer. Both genes are present in all human beings; it is changes in the genes that result in cancer.
Dr. Henry Lynch, the director of the hereditary cancer clinic at Creighton University, said he often sees women from families where breast cancer is common but where it is not being caused by BRCA1 mutations. The women, he said "are in a state of panic and anxiety when they come to see us." They suspect that some gene in their family is causing cancer and they want to know, Do they have it? "I've had to tell them that one of these days we'll get the gene for BRCA2," Dr. Lynch said.
Dr. Lynch is an author of the new paper on BRCA2, published today in Nature, a British science journal.
Cancer specialists hope BRCA2 will lead them to a new understanding of not only breast cancer families, but the many other cases of breast cancer. BRCA1 was also discovered in studies involving members of breast cancer families. But according to Dr. Mary Claire King, a molecular geneticist at the University of Washington in Seattle: "There is now increasingly good evidence that BRCA1 is involved in breast cancer in general. Now we can find out if it is true for BRCA2 as well."
Scientists said that although mutations in both BRCA2 and BRCA1 cause breast cancer, the genes are on different chromosomes, their structures seem different, and they have different effects on cancers other than breast cancer.
For example, women who inherit a mutated BRCA1 gene have a 60 percent chance of developing ovarian cancer, compared with a 20 percent chance for those with mutations in BRCA2.
On the other hand, mutations in BRCA2 in men result in a 20 percent chance of having breast cancer, whereas mutations in BRCA1 do not increase the chances of male breast cancer.
Dr. Michael Stratton, the leader of the BRCA2 study who is a molecular geneticist at the Institute for Cancer Research in Surrey, England, said that the 20 percent risk the gene confers on men is high considering that male breast cancer is so rare. According to the American Cancer Society, 1,400 cases of breast cancer in men were diagnosed this year in the United States, making male breast cancer more than 100-fold less common than breast cancer in women.
Men who inherit mutations of either breast cancer gene have an increased risk of prostate cancer. People who inherit a mutated BRCA2 gene also have a slightly increased risk of developing colon cancer, cancer of the larynx, and a malignant melanoma of the eye. Dr. Stratton cautioned, however, that "the risks of all these cancers are low." He said they are, "nothing like the breast cancer risk in women."
Dr. Stratton said that it took 12 groups of researchers in the United Kingdom, the United States, Iceland, Canada, the Netherlands and France just a year to find BRCA2, considerably faster than expected. Their work was facilitated because scientists had already begun mapping the area on chromosome 13 where the gene resides. In contrast, it took scientists four years to find BRCA1, largely because gene mappers had not yet tackled its area of chromosome 17. The work was facilitated because scientists had found the general area on chromosome 13 where the gene was located, and had begun mapping that area.
The BRCA2 gene is huge -- larger even than BRCA1, which itself had 100,000 subunits, making it 10 times larger than the average gene. That makes the search for mutations long and tedious, researchers said. Dr. Stratton said that the researchers have so far sequenced only about half of the gene.
As yet, no one has any idea what BRCA1 or BRCA2 normally do in cells.
Dr. Weber, Dr. Lynch and others said they expected to begin offering BRCA2 tests as part of research studies. But, researchers say, women should think carefully about whether they want to be tested for the breast cancer genes.
Even if a woman learns she has BRCA2 or BRCA1, Dr. Collins said, "we don't know what to tell people, we don't know what to recommend to reduce the risk of dying of cancer." Women can have frequent mammograms, hoping to catch the cancer early but investigators say they do not yet know if that will prolong the lives of women with the breast cancer genes. This is especially so because women who inherit mutated versions of either of the genes are likely to develop cancer early, while they are in their 40's, and at an age when mammograms seem less effective in finding cancer.
Dr. Collins said he worries in particular about discrimination by insurers and employers. A woman, he said, "might go through the testing, find out she's at risk, and then lose her health insurance just at the time she needs it."