Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Variations in 5 genes raise risk for most common brain tumors

07.07.2009
Genomewide study finds first genetic factors in development of gliomas

Common genetic variations spread across five genes raise a person's risk of developing the most frequent type of brain tumor, an international research team reports online in Nature Genetics.

Genetic risk factors identified by the research team, led by scientists at The University of Texas M. D. Anderson Cancer Center and the Institute of Cancer Research in the United Kingdom, also are the first glioma risk factors of any type identified in a large study.

"This is a ground-breaking study because it's the first time we've had a large enough sample to understand the genetic risk factors related to glioma, which opens the door to understanding a possible cause of these brain tumors," said co-senior author Melissa Bondy, Ph.D., professor in M. D. Anderson's Department of Epidemiology.

Bondy and colleagues expect their findings eventually to help identify people most at risk for the disease and to provide potential targets for treatment or prevention.

Gliomas, deadly tumors that form in the supportive tissue of the brain and spine, account for about 80 percent of all primary malignant brain tumors, with about 22,000 new cases annually in the United States and 13,000 deaths. They include astrocytomas, oligodendrogliomas and glioblastoma multiforme, the most aggressive, deadly and common glioma in adults.

Risk rises with each variation

The top variations in each of the five genes individually raise a person's glioma risk by 18, 24, 27, 28 and 36 percent over someone without the variations. The team found the effects are independent of one another, so risk escalates with the number of genes involved. People with eight or more of the 14 risk variations discovered on the five genes have a three-fold risk of developing glioma.

Even though this is the largest genetic study of a rare cancer, and thus provides a high degree of statistical confidence in the findings, co-first author Sanjay Shete, Ph.D., associate professor of epidemiology at M. D. Anderson, cautions that it's too early to screen people for risk using these variations alone.

Additional research is needed on the genes involved and how variation affects their function and contributes to development of gliomas. And the disease is not solely genetic. A more comprehensive model that includes demographic and behavioral factors and environmental exposures will be needed to identify those at risk.

Bondy will be principal investigator on a multi-center research project that will examine the complex interplay of all of those factors in 6,000 glioma patients and 6,000 controls beginning next year. "We will be able to look at all of the potential risk and protective factors we've identified in much smaller studies over the years, such as exposure to ionizing radiation, allergies, infections, and use of non-steroidal anti-inflammatory drugs, in a much larger study that will include the genes involved," Bondy said.

Combing through 521,571 variations to find 14

Researchers from M. D. Anderson and the Institute of Cancer Research analyzed 521,571 single nucleotide polymorphisms (SNPS) - points in the genome known to commonly vary from person to person - in 1,878 glioma patients and 3,670 controls. They discovered 34 SNPS with evidence of association with glioma.

These 34 were then analyzed in independent case-control studies in Germany, France and Sweden that examined 2,545 cases of glioma and 2,973 controls. The combined analysis winnowed the candidates down to 14 SNPS that mapped to five addresses in the genome.

The five genes identified, listed in descending order by their strongest effect, are:

CCDC26, located on chromosome 8, modulates retinoic acid, which in turn increases programmed cell death in glioblastoma cells and reduces telomerase activity (see next).

TERT, found on chromosome 5, is essential for telomerase activity that preserves telomeres, which are found on the ends of chromosomes and prevent them from unraveling. TERT expression in tumors has been associated with tumor grade and prognosis.

CDKN2A, located on chromosome 9, regulates p14, which activates the tumor-suppressor p53. It also regulates cyclin-dependent kinases vital to the cell cycle. At least one copy of the gene is deleted in half of brain tumors, and loss of CDKN2A expression is associated with poor prognosis.

RTEL1, found on chromosome 20, maintains genomic stability. Its chromosomal address is amplified in 30 percent of gliomas.

PHLDB1, on chromosome 11, is commonly deleted in neuroblastoma but there is no evidence to date of a role for the gene in glioma.

The fact that four of the genetic variations found in a person's genome point to a gene that has been associated in some way with the genome of the tumors is an encouraging sign, Shete said.

"I've been collecting families and case studies since the early 90s," Bondy said. "We have only just begun to understand the causes of brain tumors. Our findings give reasons for hope for those who might be affected and an incentive for a more comprehensive investigation of what has been a mysterious disorder."

The Wellcome Trust provided principal funding for the study. Additional sources include Cancer Research UK, the European Union, grants from the U.S. National Cancer Institute, the American Brain Tumor Association and the National Brain Tumor Society.

Co-authors with Bondy and Shete are co-senior author Richard Houlston and co-first author Fay Hoskings, Lindsay B Robertson, Sara E Dobbins, and Amy Price, all of Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey. U.K.; Georgina Armstrong, Yanhong Liu, and Xiangjun Gu of M. D. Anderson's Department of Epidemiology; Marc Sanson, Yannick Marie, Blandine Boisselier, Jean-Yves Delattre, Khe Hoang-Xuan, Soufiane El Hallani and Ahmed Idbaih, all of Service de Neurologie Mazarin et INSERM, Hôpital de la Salpêtrière in Paris; Beatrice Malmer, Ulrika Andersson and Roger Henriksson, of Department of Radiation Sciences, Oncology, Umeå University, Sweden; Matthias Simon and Johannes Schramm of Neurochirurgische Universitätsklinik, Bonn, Germany; Diana Zelenika and Mark Lathrop of Centre National de Génotypage, Evry Cedex, France; Lathrop also is affiliated with Foundation Jean Dausett-CEPH, Paris; A Tommy Bergenheim, and Anders Ahlbom of Department of Clinical Neuroscience, Umeå University, Sweden; Maria Feychting of Institute of Environmental Medicine, Karolinska Institutet, Sweden; Stefan Lönn of the Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Sweden; Michael Linnebank of the Department of Neurology, University Hospital Zurich, Switzerland; Kari Hemminki and Rajiv Kumar both of the Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany; Sarah Hepworth of Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health, University of Leeds, UK; Kenneth Muir of the Division of Epidemiology and Public Health, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK; Minouk Schoemaker Section of Epidemiology, Institute of Cancer Research, Sutton, UK; and Ching Lau of Texas Children's Cancer Center, Baylor College of Medicine, Houston.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>