Research into rare disease leads to discovery of six new breast cancer-susceptibility genes.(Brief Article)

2002 JUL 11 - (NewsRx.com & NewsRx.net) -- A decade of research into one of the world's least-known diseases has resulted in a major advance against one of the best-known: the discovery of six genes linked to inherited breast cancer.

In a study published online by the journal Science (www.sciencemag.org) on June 13, 2002, investigators at Dana-Farber Cancer Institute and Children's Hospital Boston report that an error in any of the half-dozen genes involved in Fanconi anemia - a rare childhood condition - can increase an individual's chances of developing breast cancer. The discovery raises the prospect that the ranks of known breast cancer-susceptibility genes - best known as BRCA1 and BRCA2 - will soon increase fourfold, to a total of eight.

"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," said the study's senior author, Alan D'Andrea, MD, of Dana-Farber. "Women and their doctors can then use the information in deciding how to keep that risk at a minimum."

The finding may also spur the development of new treatments capable of preventing or quelling breast cancer in women at risk for the disease. Drugs that can counteract the flaws in specific genes promise to be more effective than therapies that take a more generic approach.

The discovery of the new cancer-susceptibility genes grew out of more than 10 years of research by D'Andrea into Fanconi anemia, a condition known to affect only 500 families in the United States. Children born with the condition usually develop bone marrow failure early in life, leaving them unable to produce oxygen-carrying red blood cells. If they survive into young adulthood - often with the help of a bone marrow transplant - they're at risk for a variety of cancers - most often leukemia, but also tumors of the brain, head and neck, breast, colon, and other parts of the body.

"This work is a prime example of how research into rare conditions can lead to better diagnosis and treatment for people with far more common diseases," D'Andrea explained.

Fanconi anemia is caused by a mutation in any of six genes in human cells. In recent years, D'Andrea and other investigators have mapped out the chain of events by which these genes are switched on. When a cell's DNA is damaged - whether by excessive sunlight, chemicals such as those found in cigarette smoke, radiation or other means - five of the Fanconi genes team up to produce a protein "complex" that stimulates a sixth gene. That gene, dubbed D2, orders production of a protein that moves near BRCA1, whose job is to help repair damaged DNA.