Cancer mutation higher in Jewish women

By Susan Milius

WASHINGTON (UPI): A gene mutation that carries a high risk of breast and ovarian cancer may be three to eight times more common in Jewish women with Eastern European family roots than in the general population, researchers said Thursday.

This discovery may eventually let doctors set up the first screening tests to see if Ashkenazi Jewish women are at risk from a mutation in the BRCA1 gene, said Larry Brody from the National Center for Human Genome Research in Bethesda, Md.

He, Jeff Struewing and colleagues found a specific glitch in the Brca1 gene that appeared in almost one out of 100 Ashkenazi Jews.

Even when combining the frequency of this particular error in the BRCA1 gene -- a biological typo dropping two base pair chemicals at position 185 -- with other possible errors in the same gene, researchers estimate that only one in 300 or perhaps one in 800 women in the general population has an alarming mutation in the gene.

The research team drew these estimates from a study, published in the new issue of Nature Genetics, of DNA samples collected from 858 Ashkenazim for a different screening program. The specific mutation popped up in eight of the Ashkenazim samples, but in none of 815 other DNA samples chosen from people with a mix of family origins.

Ashkenazi Jews

Brody pointed out that the study could only pick up abundance in Ashkenazi Jews not in other tightly related groups. The mutation "may have a high frequency in other populations," he said.

Women who carry the newly identified mutation or another one in BRCA1, have an 80 percent to 90 percent risk of developing breast cancer at some point in their lives and a 40 percent to 50 percent risk of having ovarian cancer, according to the researcher's current estimates.

Factors other than genetics push tissue to turn cancerous, and Brody estimated that perhaps five percent to ten percent of breast cancers have a genetic component.

Researchers have fingered four genes as potential culprits in inherited forms of breast cancer. Brody estimated that mutations in the gene Brca1 account for two percent to three percent, and its sister gene, BRCA2, which has been localized but not cloned yet, cause another two percent or three percent.

Brody does not expect the P53 gene to have a huge role in inherited breast cancer, and he leaves as an open question the ATM gene, cloned this summer to great fanfare and high estimates of breast-cancer involvement.

Testing women for mutations in genes has proved difficult, said Brody. Even for researchers willing to devote the time and money to work through an entire gene piece-by-piece, searching for all possible mutations "is absolutely not straightforward," said Struewing. Failing to find a mutation by the current, rather delicate methods, may mean the same thing as failing to find one typo when reading an entire book: the proofreader may have overlooked something.

Short-cuts

In search of short-cuts for testing, researchers hope to find that most mutated genes have the same mistake, requiring only a fast, affordable test of the little piece of DNA likely to be damaged.

Until the new study, BRCA1 has been a tester's nightmare, with at least 50 mutations identified so far. Going through the entire gene of 5,000 chemical subunits would take two months of working in the lab, said Struewing, "assuming you were perfectly efficient and didn't get phone calls."

The mutation found in the Ashkenazi samples, however, opens the way for feasible screening for that particular genetic typo. Still, "there are a lot of thorny issues out there," warned Struewing.

Women identified with a dangerous mutation might have trouble getting insurance coverage or might scare away potential employers, said Brody.

He is also concerned that no clear medical advice exists for women who discover they have the gene. For example, surgically removing otherwise healthy breasts to forestall the disease is the most drastic option open to mutation-carriers, but doctors cannot predict in which cases preventative surgery would be sensible.

Brody's hope is that women at risk will take precautions anyway, getting mammograms, doing regular self-exams and eating sensibly.

"It's been haunting me for the last month," said Brody as he explained the implications of genetic screening. "Society's probably not quite ready for it."