Navigation Links
Newly identified markers may predict who will respond to breast cancer prevention therapy
Date:6/13/2013

PHILADELPHIA Genetic variations, known as single nucleotide polymorphisms (SNPs), in or near the genes ZNF423 and CTSO were associated with breast cancer risk among women who underwent prevention therapy with tamoxifen and raloxifene, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

Women who have the favorable variations of these two SNPs are more likely to respond to prevention therapy, according to this study. Women who have the unfavorable variations of these SNPs may not benefit from prevention therapy, and they have a five-fold increased risk of developing breast cancer.

"The recent guidelines by the U.S. Preventive Services Task Force emphasize that selective estrogen receptor modulator (SERM) therapy with tamoxifen and raloxifene can lower a woman's risk for developing breast cancer. But about 50 women have to be exposed to the treatment and side effects to prevent a single case of breast cancer," said James N. Ingle, M.D., professor of oncology at the Mayo Clinic in Rochester, Minn.

"Our findings are important, because for the first time, we discovered genetic factors that could be used to select women who should be offered the drugs for prevention. Also of substantial importance is that we have discovered new information on how tamoxifen and raloxifene work to prevent breast cancer."

Ingle and his colleagues at the Mayo Clinic, along with researchers at the National Surgical Adjuvant Breast and Bowel Project (NSABP) in Pittsburgh, Pa., and the RIKEN Center for Genomic Medicine in Tokyo, Japan, conducted a genome-wide association study involving 592 patients who developed breast cancer while on SERM therapy and 1,171 matched controls. They selected participants from the 33,000 women enrolled in the NSABP P-1 and P-2 breast cancer prevention trials.

He and his colleagues analyzed participants' DNA using the Illumina Human610-Quad BeadChip to identify variations in their genetic makeup. They identified two SNPs that were most relevant to breast cancer risk, one in the gene ZNF423, and the other near the gene CTSO.

"Our discovery is a major step toward truly individualized prevention of breast cancer. Findings from our study provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene," said Ingle. "The best chance we have of decreasing the burden of breast cancer is to prevent it in the first place. Our findings provide the basis for a reinvigoration of research efforts in breast cancer prevention."

The researchers conducted further experiments using breast cancer cell lines harboring either the most common variation or the less common variation of the SNPs. They found that in cells with the most common variation of the SNPs, estrogen increased expression of both ZNF423 and CTSO, as well as expression of BRCA1, a gene related to breast cancer risk. Estrogen did not increase expression of these genes in cells that had the less common form of the SNPs.

When tamoxifen or raloxifene were added to estrogen, there was a striking reversal in the patterns of expression of ZNF423 and BRCA1. In cells with the less common ZNF423 SNP, expression of ZNF423 and BRCA1 rose dramatically. This reversal in expression patterns provides a potential explanation for the decreased occurrence of breast cancer in women undergoing SERM therapy who carry this SNP.

In addition, the researchers found that the different forms of the ZNF423 and CTSO SNPs predicted the odds for developing breast cancer while undergoing SERM therapy: Women who had the favorable variations of both the SNPs had the lowest risk and women who had the unfavorable variations of both the SNPs had a more than five-fold relative increased risk for developing breast cancer.


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Offer Newly Designed hCG Diet Plans that Aid Patients in Receiving Improved Medical Care
2. Surrogacy matching and legal services law firm, Creative Family Connections LLC, launches newly redesigned website
3. Da Vinci Lawsuit News: Bernstein Liebhard LLP Comments on Recommendations in Newly Published Study to Reduce Robotic Surgery Complications
4. Newly-Launched TemplateHaven.com Unveils Complimentary Retirement Savings Calculator
5. MessageSolution Showcases its Newly Released Enterprise Archive and eDiscovery Platform 7.0 at Tech Expo, Supporting Microsoft Exchange and SharePoint 2013
6. Bevacizumab offers no benefit for newly diagnosed glioblastoma, M.D. Anderson-led study finds
7. hCG Treatments/Diet Doc hCG Diets & Weight Loss Plans Offers Newly Improved hCG Diet Plans Thought To Reduce Menopausal Weight Gain and Its Related Symptoms
8. Myrtle Beach Urology Groups Administer First Commercial Dose of Newly FDA Approved Prostate Cancer Treatment
9. Wireless Analytics Responds to Newly Released TEMIA “BYOD Dos and Don’ts” White Paper
10. hCGTreatments / Diet Doc hCG Diets & Weight Loss Plans Announces Newly Improved hCG Diets Offering Its Best Weight Loss and Reducing Risks of Cardiovascular Disease
11. Great Healthworks, Inc, Makers of Omega XL, Report Newly Published Study on Their Patented Oil: PCSO-524® Delivers Relief for Delayed Onset Muscle Soreness
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/23/2017)... (PRWEB) , ... May 23, 2017 , ... ... Plastic and Reconstructive Surgeon Dr. Kevin Sadati, is pleased to announce a new ... building collagen and elastin in their face, neck, and body through a virtually ...
(Date:5/23/2017)... ... May 23, 2017 , ... Diagnotes, an Indianapolis-based ... standard feature on its secure clinical communication platform. The platform allows clinicians to ... on the type and urgency of a situation. , “We know from ...
(Date:5/23/2017)... ... May 23, 2017 , ... New patients looking ... System™ Orthodontics, with or without a referral, from the multi-specialty Dr. Smile practice. ... who is skilled in providing patients with the custom, convenient and long-lasting orthodontic ...
(Date:5/22/2017)... ... May 22, 2017 , ... Patients who avoid necessary dental and ... dentistry in Mt. Kisco, NY from Advanced Endodontics of Westchester. This highly-trained team of ... treatments. One or more sedation methods may be recommended based on the severity of ...
(Date:5/22/2017)... ... 22, 2017 , ... “Homeostasis: The Journey of a Manic-Depressive” tells the story ... Donald Rodriguez takes readers on a rollercoaster ride that includes a midnight trek to ... to a dark place where Donald considers suicide. Readers learn how Donald finally ...
Breaking Medicine News(10 mins):
(Date:5/9/2017)... May 9, 2017  Semler Scientific, Inc. (OTCQB: ... solutions to improve the clinical effectiveness and efficiency ... the first quarter ended March 31, 2017. ... our customers to identify when preventive care options ... events like heart attacks or strokes occur," said ...
(Date:5/6/2017)... is Stroke Awareness Month and Omron Healthcare is reminding ... prevent a stroke: monitor and manage your blood pressure. ... undetected and uncontrolled hypertension is a leading risk factor ... personal heart health technology, recently evolved its mission to ... and is advancing a national public education effort to ...
(Date:5/4/2017)... , May 4, 2017 Clarius ... its wireless, handheld ultrasound scanners this week at ... Scientific Meeting (ACOG) in San Diego, ... "Clarius is the perfect tool for ... and heart rate, and evaluate pregnancy-related complications like ...
Breaking Medicine Technology: