Study adds piece to genetic puzzle.

2002 OCT 17 - (NewsRx.com & NewsRx.net) -- The pieces of a genetic puzzle are starting to come together. Earlier this year, University of Iowa Health Care researchers determined that a gene known as BRCA1 plays a more extensive role in ovarian cancer than previously thought. Now, they have determined the same is true for the BRCA2 gene.

The findings point to the importance of developing therapies to restore normal BRCA2 and/or BRCA1 function in women with ovarian or fallopian cancer or a related cancer known as primary peritoneal cancer. The study results appear in the September 18, 2002, issue of the Journal of the National Cancer Institute.

The UI team looked for BRCA2 dysfunction in the tumors of 92 women who had been the focus of the earlier BRCA1 study. The investigators found that 82% of the tumors had dysfunctional BRCA1 or BRCA2.

The high incidence rate contrasts dramatically with the BRCA1 and BRCA2 dysfunction rates previously associated with ovarian cancer, said Richard Buller, MD, PhD, UI professor of obstetrics and gynecology, and the study's principal investigator.

"As recently as 2 to 3 years ago, people thought only 5-10% of ovarian cancer cases had disrupted BRCA1 or BRCA2 function, and most of those dysfunctional genes were thought to be inherited," said Buller, who also is a professor of gynecologic oncology at the Holden Comprehensive Cancer Center at UI. "However, together the two studies show frequent BRCA2 and BRCA1 dysfunction in sporadic, or nonhereditary, ovarian cancers, not just in a portion of hereditary ovarian cancers.

"With that level of dysfunction, therapies targeted toward the return of BRCA1 and BRCA2 function are very important for virtually every woman with ovarian or a related cancer," he added.

In hereditary ovarian cancer, women inherit a faulty gene, and thus their ovarian cancer often is linked to a family history of the disease. In sporadic ovarian cancer, a woman's pair of BRCA1 or BRCA2 genes initially functions well but becomes nonfunctional through a number of ways, including when one or both genes are lost or mutated.