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.