May 30, 1996
30 May 1996: Mutations of Gene BRCA2 Responsible for Few Sporadic Cases of Breast Cancer, NIEHS And Duke Report
Mutations of the breast cancer gene BRCA2, like those of the first-identified BRCA1, seldom appear to be involved in sporadic, non-inherited breast cancer and ovarian cancer-the 95 percent that does not run in families.
These results were reported today in the June issue of the journal Nature Genetics by British physician Johnathan Lancaster, a research fellow at the National Institute of Environmental Health Sciences, a part of the National Institutes of Health, and Andrew Futreal of Duke Comprehensive Cancer Center, as well as the Institute of Cancer Research in Surrey, UK. In their study of 70 sporadic breast cancers and 55 ovarian cancers, the scientists found alterations of the gene in only two of the breast cancers and none of the ovarian cancers.
Some of the same Duke and NIEHS researchers reported last month that BRCA2 was linked to fewer inherited breast cancers than had been predicted before the gene was isolated. This additional finding that its mutations are seldom found in sporadic breast cancer might be seen as reducing the importance of BRCA2, but Dr. Lancaster said that finding few mutations does not necessarily mean that BRCA2 has no role in sporadic breast cancers, but that something other than classic mutations of this gene may be responsible.
"Mutations are not the only way that BRCA2 could be involved," Dr. Lancaster said. "As we are discovering with BRCA1, the gene may be implicated in sporadic disease by changes in the amount of its protein or even the site of that protein within the cell, so that the gene, though of normal sequence and structure, does not suppress breast cancer as it should."
"Both BRCA1 and BRCA2 are large, complex genes," he said, "and few of their mysteries have been discovered so far."
Dr. Lancaster's current research home is the laboratory of molecular carcinogenesis at NIEHS, which is an institute of the National Institutes of Health. NIH is headquartered in Bethesda, Md., and most of its institutes are there but NIEHS has its own 509-acre campus in Research Triangle Park, N.C., a major center of environmental and health-related research.
Dr. Futreal was a key member on the NIEHS team and subsequently, heading his own lab at Duke, was a principal investigator in the identification of BRCA2 last December. Dr. Lancaster was also a member of the international BRCA2 identification team.
Other authors of the current research include Catherine M. Phelan, Curtis Gumbs, Andrew Berchuck, J. Dirk Iglehart and Jeffrey R. Marks of Duke, Richard Wooster, Johnathon Mangion, Sheila Seal, Rita Barfoot, Nadine Collins, Graham Bignell, Sandeep Patel, Rifat Hamoudi, Alan Ashworth and Michael Stratton, all of the Institute of Cancer Research in Surrey, England; Roger Wiseman and Charles Cochran, NIEHS; and Catharina Larsson, Karolinska Hospital, Stockholm.
NIEHS' research interests include the human being's varying susceptibility to substances in the environment that may contribute to cancer. This interest has led to its involvement in the discoveries of the breast cancer/ovarian cancer genes, BRCA1 and BRCA2, and the prostate cancer suppressor gene.
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