Fanconi anemia and cancer
The researchers were curious. Dr. Alan D'Andrea, of Dana-Farber Cancer Institute in Boston, Massachusetts, and Dr. Markus Grompe, of Oregon Health Sciences University in Portland, Oregon, had been studying children with Fanconi anemia, an inherited disorder that causes bone marrow failure. While many of these children were helped by receiving bone marrow transplants, they often developed cancer as they grew older, usually leukemia but also tumors of the brain, head and neck, or esophagus. The question in the doctors' minds was, Why did these children seem to be so susceptible to a wide range of cancers?

In the course of their research, the doctors identified seven genes involved in Fanconi anemia. The research showed that proteins produced from five of those genes activated a sixth gene, which they named FANCD2. Further research demonstrated that, once activated, FANCD2 produces a protein that switches on another gene, one the researchers didn't expect was involved--the BRCA1 gene.

The role of BRCA1
BRCA1 was the first breast cancer gene identified, and it causes about 5% of the 180,000 cases of breast cancer diagnosed in the United States each year. Research about the gene shows that BRCA1 plays a much larger role in the body, though. "There's strong evidence that under normal conditions, BRCA1 helps repair DNA damage in cells, preventing the cells from becoming cancerous," Dr. D'Andrea stated recently. "But until now, little was known of how BRCA1 is switched on. This new study presents a pathway leading to BRCA1 activation--and it was discovered by studying a condition that's known to affect only 500 families in the United States."

In other words, switching on the BRCA1 gene is good, since it helps prevent cancer. In healthy people, all of the Fanconi genes work correctly, leading to the activation of BRCA1. In Fanconi anemia, though, one or more of those six genes doesn't work correctly, and fails to produce the right protein, therefore breaking the chain of events leading up to the activation of BRCA1. Since BRCA1 isn't activated, cell damage that occurs may not be repaired by the body, and cancer may start forming.

Future research
Discovering the links between the Fanconi genes and BRCA1 seems to hold potential for future cancer research. If a mutation in one of the Fanconi genes blocks the normal activation of BRCA1, then testing for those mutations might help identify women at risk for breast cancer. Dr. D'Andrea's findings also support what genetics researchers have long suspected--that diseases and conditions are not caused by just one gene, but instead come from the interactions of different genes and their proteins.

Another avenue for future research would be examining the particular gene "pathway" in Fanconi anemia--the sequence of genes and proteins leading to BRCA1 activation. "It might be possible to design a drug that amplifies this pathway, accelerating the repair work of BRCA1 and reducing the chances that breast cancer will occur in people with a genetic risk for it," D'Andrea said. "Much work, however, remains to be done before such therapies become a reality."

Information for this article was taken from:
- Fox, Maggie. "A Rare Disease Gives Clues to Cancer Genes," The Boston Globe, February 16, 2001.
- "Scientists Discover 'Missing Link' Between Rare Disease And - Inherited Forms of Breast Cancer," Science Daily, February 16, 2001.

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