Gene variants to predict women benefitting from breast cancer prevention drugs
Washington: Researchers have identified two gene variants that may predict which women are likely to benefit from a long-term drug treatment that can cut the risk of developing the disease in half.
The work represents a major step toward truly individualized breast cancer prevention in women at high risk for the disease based on their age, family history of breast cancer, and personal medical history.
The study`s lead scientist, James N. Ingle, M.D., professor of oncology at the Mayo Clinic in Rochester, Minnesota, said that their study reveals the first known genetic factors that can help predict which high-risk women should be offered breast cancer prevention treatment and which women should be spared any unnecessary expense and risk from taking these medications.
He said that they also discovered new info about how the drugs tamoxifen and raloxifene work to prevent breast cancer.
Ingle and Mayo-based colleagues in the NIH Pharmacogenomics Research Network (PGRN) conducted the study in collaboration with PGRN-affiliated researchers at the RIKEN Center for Genomic Medicine in Tokyo.
Data and patient DNA came from the long-running National Surgical Adjuvant Breast and Bowel Project (NSABP), supported by the National Cancer Institute.
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 SNPs-one in a gene called ZNF423 and the other near a gene called CTSO.
Neither ZNF423 nor CTSO-nor any SNPs related to these genes-had 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 act by affecting the activity of BRCA1, a known breast cancer risk gene. Healthy versions of BRCA1 reduce disease by repairing a serious form of genetic damage. Harmful versions of BRCA1 dramatically increase a woman`s chance of developing breast cancer.
The research has been published in Cancer Discovery.
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