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Gene variants may predict who will benefit from breast cancer prevention drugs
Date:6/13/2013

going breast cancer preventive treatment take tamoxifen or raloxifene for five years. In rare cases, the drugs can cause dangerous side effects, including blood clots, strokes and endometrial cancer.

Many women never try the therapy because the chance of success seems small (about 50 women in the NSABP trials needed to be treated to prevent one case of breast cancer) compared to the perceived risk of side effects. More women might benefit from the potentially life-saving strategy if doctors could better predict whether the therapy was highly likely to work. That's what the current study begins to do.

The investigators leveraged data from past NSABP breast cancer prevention trials that involved a total of more than 33,000 high-risk womenthe largest sets of such data in the world. Women in the trials gave scientists permission to use their genomic and other information for research purposes.

The scientists analyzed the genomic data by focusing on more than 500,000 genetic markers called single nucleotide polymorphisms (SNPs). Each SNP represents a single variation in the DNA sequence at a particular location within the genome.

To determine whether any SNPs were associated with breast cancer risk, the researchers computationally searched for SNPs that occurred more commonly in women who developed breast cancer during the trial than in women who remained free of the disease. The analysis identified two such SNPsone in a gene called ZNF423 and the other near a gene called CTSO.

Neither ZNF423 nor CTSOnor any SNPs related to these geneshad previously been associated with breast cancer or response to the preventive drugs. The scientists' work revealed that women with the beneficial version of the two SNPs were 5.71 times less likely to develop breast cancer while taking preventive drugs than were women with neither advantageous SNP.

Using a variety of biochemical studies, the scientists learned that ZNF423 and CTSO ac
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Contact: Alisa Z Machalek
alisa.machalek@nih.gov
301-496-7301
NIH/National Institute of General Medical Sciences
Source:Eurekalert

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