THURSDAY, June 13, 2002 (HealthDayNews) -- In the process of studying a rare disease called Fanconi anemia, scientists have made some important discoveries about breast cancer risk.
They've identified six new breast cancer-susceptibility genes that may help doctors and their patients better assess the risk of getting the disease.
The discovery was made after a decade of research on Fanconi anemia (FA), a childhood disorder that makes people more susceptible to cancers such as acute myeloid leukemia and head and neck cancers. Children born with the condition usually develop bone marrow failure early and may need a bone marrow transplant.
Researchers had suspected a link between the six genes so far identified in Fanconi anemia and the so-called breast-cancer susceptibility genes, BRCA1 and BRCA2, which have been known about for years.
So they evaluated cell lines from patients with Fanconi anemia. And they found that an error in any of the six known FA genes can increase a woman's chance of getting breast cancer.
"None had mutations in BRCA1," says Alan D. D'Andrea, a professor of pediatrics at Harvard Medical School and the senior author of the study, published today in the online issue of Science. But they did find mutations in BRCA2.
Based on the finding, the known breast cancer-susceptibility genes now total eight. BRCA1 and BRCA2 genes are thought to be linked to only a small number of breast cancer cases, according to the American Cancer Society.
The team discovered that chromosomes from breast cancer cells had a type of breakage that is similar to cells from Fanconi anemia patients. In the lab, genetics experts couldn't tell the cells apart, strengthening the suspicion. Defects in BRCA1 and BRCA2 and in the Fanconi genes make it impossible to repair a cell's DNA when it is damaged by such toxins as chemicals from cigarette smoke, radiation, or excess sunlight, increasing vulnerability to cancer.
The practical ramifications? "The supposition is that only 5 percent of breast cancer patients have mutations in BRCA1 or BRCA2," D'Andrea says. "Now it's reasonable to think some of the other 95 percent may have mutations in the other six Fanconi anemia genes."
The finding may help doctors and women better evaluate their breast cancer risk. "Just as women today can be tested for BRCA1 and BRCA2 mutations to determine if they have an inherited predisposition for breast cancer, testing for mutations in these other six genes may soon become a routine part of gauging inherited breast cancer risk," D'Andrea says in a prepared statement from the Dana-Farber Cancer Institute, a teaching affiliate of Harvard Medical School.
The therapeutic applications of the discovery are further off, he says in an interview. But someday, the hope is to use genes to replace the defective ones, or to develop drugs to strengthen the defective DNA repair pathway.
Because those diagnosed with Fanconi anemia are at high risk of cancer, "we always figured it would have some connection with cancer in the general population," D'Andrea says. "We didn't expect it would link up with BRCA1 and BRCA2."
Fanconi anemia, an inherited disorder, can result from mutations in at least eight individual genes, research has found. Now, with the new study, it's known that one of the previously unidentified genes is in fact BRCA2. Previous research had found an interaction between Fanconi anemia and BRCA1.
In a perspective piece accompanying the report, Emily Witt and Alan Ashworth from the Institute of Cancer Research in London note that "only a small portion of the cases of Fanconi anemia, which in itself is rare, is caused by the BRCA2 mutation. But the importance of this finding is that it connects two previously different bodies of work on DNA repair." They add that it will further understanding of both diseases.
Another expert, Dr. Donald Kohn, a professor of pediatrics at the University of Southern California Keck School of Medicine and at the division of research immunology/bone marrow transplant at Childrens Hospital Los Angeles, says of the study: "It's very interesting because the function of BRCA1 and [BRCA]2 genes is not fully understood. BRCA1 and [BRCA]2 mutations can predict an increased risk of breast cancer, but can't tell a woman with certainty whether she will get it."
The new report, he says, sheds more light on the interaction between environmental toxins and risk factors you inherit. Those with a defective gene don't have the same ability as others to repair the DNA damage caused by chemicals from cigarettes, radiation, and other toxins.
Based on the study, Kohn stops short of making any recommendations. But he does suggest that relatives of people with any form of Fanconi anemia "should at least talk to their doctor about it to see if they should be tested for BRCA1 and BRCA2." Just as important, he says, is to minimize exposure to environmental toxins such as cigarette smoke.
What To Do
For more on Fanconi anemia, try the Fanconi Anemia Research Fund. For more on BRCA1 and BRCA2 mutations, visit the American Cancer Society.
