WASHINGTON--University of Pennsylvania researchers have obtained the first "conclusive" evidence linking mutations in the recently cloned BRCA2 breast cancer gene to ovarian cancer, a discovery they say indicates that inheritance plays a significantly greater role in the disease than previously thought.
An anomaly of the study was that some women with inherited BRCA2 mutations in their ovarian tumors did not have a family history of either breast or ovarian cancer, and, unlike women with the BRCA1 mutation, who tend to have early onset disease, they generally developed their cancers after age 60.
Linkage studies and pedigree analyses have suggested that inherited mutations of BRCA2 account for up to 50% of all hereditary breast cancer cases "and a much smaller, but as yet undetermined fraction of hereditary ovarian cancer cases," Jeffrey A. Boyd, PhD, said at a press briefing at the American Association for Cancer Research meeting.
Dr. Boyd and his colleagues set out to determine the extent of the gene's involvement in ovarian cancer. They examined the BRCA2 region on chromosome 13 in tumors obtained from 130 consecutive, unselected ovarian cancer patients treated at the University of Pennsylvania Medical Center, Philadelphia, where Dr. Boyd is director of the Gynecologic Oncology Research Laboratory.
Approximately 45% of those cancers displayed loss of heterozygosity at polymorphic markers that overlapped the BRCA2 locus, Dr. Boyd reported, including five frameshift mutations and one missense mutation. "This suggests that approximately 5% of all ovarian carcinomas contain BRCA2 mutations," he said.
Original Estimates Too Low?
Prior to this study, research based on estimates derived from familial clustering and unusual medical histories had suggested that an inherited predisposition played a role in 5% to 10% of all ovarian cancers.