Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research team discovers genetic variance in cancer protection from statin drugs

22.04.2010
Findings should help personalize use of the drug, NewYork-Presbyterian/Weill Cornell scientists say

Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have discovered why statins -- popular drugs that lower cholesterol and appear to protect against colorectal cancer development -- work for some people, but not for all.

In the May issue of Cancer Prevention Research, the researchers say that, based on their study, about 44 percent of Caucasians taking statins likely are not protected against cancer as well as others because they have inherited a particular gene variant. They say this finding might help personalize the use of statins, both by offering patients a test to determine if they have the "right" gene to benefit from current statin drugs, and by providing insight into how to create a new class of statins for those who have the "wrong" gene profile.

"Given that approximately 25 million individuals worldwide currently use statins, we anticipate this discovery may prompt development of more precise, personalized and cost-effective cancer risk reduction strategies," says the study's co-lead author, Dr. Steven M. Lipkin, associate professor of medicine and of genetic medicine at Weill Cornell Medical College and a geneticist and internist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

The other lead author is Dr. Stephen B. Gruber, professor of internal medicine, epidemiology and human genetics at the University of Michigan Medical School. The research team also includes scientists from the University of Barcelona, the National Cancer Institute and the Israel Institute of Technology.

The researchers tested their hypothesis that people who don't respond well to the cholesterol-lowering ability of statins also do not benefit from recently documented protective effects of statins against colorectal cancer, and that the difference was in genetic variation that led to a different response to the drug.

In this study, the research team genotyped 40 candidate genes known to be important for synthesis and metabolism of cholesterol in people who participated in a population case-control study of colorectal cancer in northern Israel. Included were 1,780 colon cancer patients and 1,863 people who did not have colorectal cancer, and many of the participants, who were predominantly Caucasian, had used statins for a long time. In the initial study, statin use was associated with a 50 percent relative risk of developing colorectal cancer in this population.

Included in the 40 genes were six SNPs, or DNA sequences, within the HMGCR gene, which produces a critical enzyme involved in formation of cholesterol.

They found one SNP within HMGCR that was associated with statin protection against colorectal cancer. A follow-up pharmacogenetic analysis showed that the protective association was significantly stronger among individuals with what they dubbed the "A" SNP allele, or variant, compared with people who had a "T" variant. Because a person inherits two variants, one from each parent, the stronger colorectal cancer protection came from individuals with the A/A HMGCR genotype, compared with those with the T/T genotype. Individuals with an A/T genotype had intermediate protection against colorectal cancer -- levels that varied between that seen for A/A and T/T genotypes.

Dr. Lipkin estimates that, in this Caucasian population, 56 percent had at least one A allele in that HMGCR genomic position.

They then tested, in laboratory colorectal cancer cells, why the T allele might not work well with statins, and found that the protein produced by this HMGCR gene variant does not bind on to the statin like the A allele does, due to "alternative splicing" -- the production of a protein that is slightly altered.

"Carriers of the A allele express more of the full-length protein that binds statins, and are therefore more sensitive to statins and are more likely to experience the colorectal cancer risk reduction associated with long-term use. That is especially true if a person has two A alleles," says Dr. Lipkin. "Carriers of the T allele are less sensitive to statins because they are missing part of the protein that binds to statins. A protective effect against colorectal cancer development is largely absent from people who have two T alleles."

"Together, these studies provide strong evidence that these two alleles play an important role in modulation of HMGCR activity for colorectal risk reduction," Dr. Lipkin says. "We anticipate that genotyping for these alleles in patients may help identify those who are most likely to benefit from statins, and spare others who will not respond from any side effects of the drugs."

Dr. Lipkin believes most of the many statin drugs on the market work by binding on to the HMGCR protein. Most of the participants in this study used simvastatin (marketed under the trade names Zocor, Simlup, Simcard, Simvacor, and others), and pravastatin (marketed as Pravachol or Selektine).

The study was funded by the National Cancer Institute, a University of Michigan Cancer Center Support grant, the Spanish Secretaria de Estado de Universidades e Investigación, and the Ravitz Foundation.

For more information, patients may call (866) NYP-NEWS.

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances -- including the development of the Pap test for cervical cancer; the synthesis of penicillin; the first successful embryo-biopsy pregnancy and birth in the U.S.; the first clinical trial for gene therapy for Parkinson's disease; the first indication of bone marrow's critical role in tumor growth; and, most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian/The Allen Hospital. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar.

Andrew Klein | EurekAlert!
Further information:
http://www.med.cornell.edu
http://www.nyp.org

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>