Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Two Gene Variants May Predict Who Will Benefit from Breast Cancer Prevention Drugs

Published: Friday, June 14, 2013
Last Updated: Friday, June 14, 2013
Bookmark and Share
NIH-supported discovery could advance individualized care of high-risk women.

In women at high risk for breast cancer, a long-term drug treatment can cut the risk of developing the disease in half.

Researchers supported by the National Institutes of Health have now identified two gene variants that may predict which women are most likely to benefit from this therapy - and which should avoid it.

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.

"Our 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," said the study's lead scientist, James N. Ingle, M.D., professor of oncology at the Mayo Clinic in Rochester, Minn.

Ingle continued, "We also discovered new information 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.

"This innovative, PGRN-enabled international research partnership has produced the first gene-based method to identify which women are likely to benefit from a readily available preventive therapy," said PGRN director Rochelle Long, Ph.D., of the NIH's National Institute of General Medical Sciences. "Because the disease affects so many women worldwide, this work will have a significant impact."

The research, which shows nearly a six-fold difference in disease risk depending on a woman's genetic makeup, appears in the June 13, 2013, issue of Cancer Discovery.

Women undergoing 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 women - the 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 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 results of our collaborative research bring us a major step toward the goal of truly individualized prevention of breast cancer," said Ingle. "Our findings also underscore the value of studying the influence of gene variations on drug responses."


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Tuesday, April 12, 2016
Decoding Ties Between Vascular Disease, Alzheimer’s
NIH consortium uses big data, team science to uncover complex interplay of factors.
Tuesday, March 15, 2016
Researchers Find Link Between Death of Tumor-Support Cells and Cancer Metastasis
Researchers at NIH have found that the lifespan of supportive cells in a tumor may control the spread of cancer.
Tuesday, February 23, 2016
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH-funded study could lead to new tick control methods.
Tuesday, February 09, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Thursday, February 04, 2016
Genome-Wide Study Yields Markers of Lithium Response
An international consortium of scientists has identified a stretch of chromosome that is associated with responsiveness to the mood-stabilizing medication lithium among patients with bipolar disorder.
Monday, February 01, 2016
Schizophrenia’s Strongest Known Genetic Risk Deconstructed
Suspect gene may trigger runaway synaptic pruning during adolescence – NIH-funded study.
Thursday, January 28, 2016
NIH Genome Sequencing Program Targets the Genomic Bases of Common, Rare Disease
The National Institutes of Health will fund a set of genome sequencing and analysis centers whose research will focus on understanding the genomic bases of common and rare human diseases.
Friday, January 15, 2016
Three Glaucoma-Related Genes Discovered
NIH-funded genetics analysis of glaucoma is largest to date.
Tuesday, January 12, 2016
International Study Reveals New Genetic Clues to AMD
NIH-funded research provides framework for future studies of AMD biology, therapy.
Tuesday, December 22, 2015
Dementia Linked to Deficient DNA Repair
Mutant forms of breast cancer factor 1 (BRCA1) are associated with breast and ovarian cancers but according to new findings, in the brain the normal BRCA1 gene product may also be linked to Alzheimer’s disease.
Tuesday, December 01, 2015
Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Scientific News
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
Autism, Cancer Share a Remarkable Number of Risk Genes
Researchers with the UC Davis Comprehensive Cancer Center, MIND Institute identify more than 40 common genes.
Number Of Known Genetic Risk Factors For Endometrial Cancer Doubled
An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.
Genetic Variant May Help Explain Why Labradors Are Prone To Obesity
A genetic variation associated with obesity and appetite in Labrador retrievers – the UK and US’s favourite dog breed – has been identified by scientists at the University of Cambridge. The finding may explain why Labrador retrievers are more likely to become obese than dogs of other breeds.
How Scientists Use DNA to Track Disease Outbreaks
They’re the top questions on everyone’s mind when a new disease outbreak happens: where did the virus come from? When did this happen? How long has it been spreading in a particular country or group of people?
Genetic Risk Factors of Disparate Diseases Share Similar Biological Underpinnings
Penn Institute for Biomedical Informatics and colleagues identify "roadmap" of disease mechanisms to identify candidate drug targets.
Stem Cells Know How to Unwind
Research led by the Babraham Institute with collaborators in the UK, Canada and Japan has revealed a new understanding of how an open genome structure supports the long-term and unrestricted developmental potential in embryonic stem cells.
Childhood Asthma Research Receives $2M
Research into the impact of a child’s upbringing and social and physical environments on the development of asthma will receive $2 million to tackle the condition that affects as many as one in three Canadians.
Five New Breast Cancer Genes Found
Discovery of mutations paves the way for personalised treatment of breast cancer.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!