BRCA Mutations Don't Raise Breast Cancer Risk Equally

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By Amanda Gardner
HealthDay Reporter
Tuesday, January 8, 2008; 12:00 AM

TUESDAY, Jan. 8 (HealthDay News) -- Not all carriers of the BRCA1 and BRCA2 genetic mutations show the same risk for developing breast cancer.

In fact, a new study finds wide variation in risk among families carrying the mutations, indicating that the mutations are influenced by other genetic, and possibly environmental, factors.

"Risk among carriers varies considerably, and, if you accept that that's the case, there must be a reason why it varies, and the most plausible explanation is that there are other genetic factors affecting breast cancer risk that are being passed on through these families," said study author Colin Begg, chairman of the department of epidemiology and biostatistics at Memorial Sloan-Kettering Cancer Center in New York City.

And that's where more work needs to be done, said Begg, whose report was published in the Jan. 9/16 issue of theJournal of the American Medical Association.

"They're saying that not all BRCA mutations are created equal," added Dr. Len Lichtenfeld, deputy chief medical officer at the American Cancer Society.

It is known that the BRCA1 and BRCA2 gene mutations raise a woman's risk for developing breast cancer, so the degree of that risk is critical in helping a woman make choices about prevention.

But most previous studies have only looked at overall risk among mutation carriers, not individual risk or risk in specific groups.

"To some extent, people have traditionally perceived the risk as being a fixed thing," Begg said. "People have studied BRCA1 and 2 separately, but, other than that, there's the sense that if you're a carrier, you have a certain risk, and it's a high risk, and that's it."

Experts have hypothesized that there is variation in the risk of breast cancer in general due to other, as yet unknown, genetic factors, but there's scant evidence of such a variation. There has been no research on whether such variation exists among BRCA mutation carriers.

This study provides such evidence.

Begg and his colleagues genotyped more than 2,000 participants in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study who had been diagnosed with breast cancer. Of the total, 1,394 women had unilateral breast cancer (one breast only), while 704 had contralateral breast cancer (an additional malignancy in the opposite breast).

This study focused on the 181 women who were shown to be mutation carriers.


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