WASHINGTON _ Almost one year to the day sinceBRCA1 _ the breast cancer gene _ was isolatedresearchers now are able to point with authority to a linkbetween a certain ethnic group which is predisposed todeveloping breast cancer and its genetic history. (SeeBioWorld Today, Sept. 15, 1994, p. 1.)

Scientists from the National Institutes of Health (NIH) incollaboration with teams of researchers around the worldsaid on Thursday that Eastern European Ashkenazi Jewshave a specific mutation in the BRCA1 gene.

The NIH said the finding "offers the first evidence from alarge study that an alteration" in the BRCA1 gene "ispresent in measurable levels not only in families at highrisk for the disease, but in a specific group of the generalpopulation."

Researchers followed the genetic trail back to EasternEuropean Jews by testing 858 DNA samples. Leadresearcher Jeffery Struewing, senior research investigatorat the NIH, told BioWorld Today that since theidentification of BRCA1 last year, scores of reports in themedical literature have appeared describing mutations inthis gene "that occur from the beginning to the end of thisgene but in no one particular hot spot."

Struewing said 60 mutations were identified in more than150 families or individuals. Of the 60 mutations, morethan 40 were found in only one family.

Previously NIH researchers focused on families with highrates of breast and ovarian cancer. In 10 of the families,three had exactly the same mutation and interestinglywere Eastern European or Ashkenazi Jews. "This led usto wonder if this particular mutation may account for themajority of mutations in this genetic sub-population.Other researchers have also found this mutation," he said.

The researchers independently observed a specific, two-base deletion called 185delAG. It was found in theBRCA1 genes of 10 families with histories of breast andovarian cancer.

Struewing said it was "not surprising that one mutationcan account for this given the cultural and historicalbackground of modern day Ashkenazi Jews who aredescended from a relatively small number of individuals."

Members of these families were found to have a carrierrate for the 185delAG deletion that is at least three timeshigher than the estimated carrier rate for all BRCA1mutations contained in the general U.S. population.

The NIH researchers estimate that the deletion mightaccount for as much as 16 percent of breast and 39percent of ovarian cancers in Ashkenazi Jewish womenage 50 and under. By comparison, the BRCA1 alterationscontribute to 4 percent of breast and 12 percent of ovariancancers in the general U.S. population

The identification of the ethnic link to breast cancerprompted the NIH to announced that it will launch aseries of clinical studies to evaluate the cancer risk inAshkenazis bearing the mutation. The results of thesestudies will help to determine whether BRCA1 testingshould be offered to the nation's six million AshkenaziJews as part of their regular health care screening.

But the study's authors stopped short of recommendingimmediate BRCA1 testing. "All along we were interestedin doing a study that was population-based but it is timeconsuming and labor intensive to detect all the possiblemutations in BRCA1," Struewing said.

Screening 5,000 Could Take A `Week Or Two'

However, the technology may now exist to screen largenumbers of individuals. "It is technically relatively simpleto screen a large number of individuals for this mutation.Previously, the thought of analyzing a large population orthe underlying carrier for all mutations was technicallyunfeasible. To analyze an entire gene of 5,000 individualswould have taken too long," he said.

"But now, if the association holds up, if this mutationaccounts for 80 or 90 percent of mutations in Jewishindividuals, then it would only take a week or two ofwork to test 5,000 people, " Struewing said.

He cautioned that although the genetic screening wouldbe technically feasible, still to be addressed are theequally perplexing questions of genetic testing on a largescale.

"Population-based studies on the genetic level arebecoming a real possibility and may help pinpoint whichgroups of people have an inherited susceptibility tocertain disease," said Frances Collins, director of theNational Center for Human Genome Research, ofBethesda, Md. "But as our knowledge of human geneticsgrows, so too does the possibility of geneticdiscrimination in employment and health insurance. Thisfinding only underscores society's need to address thesecritical issues." n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.