(Press-News.org) October 5, 2010 – Radiation therapy is used to treat more than half of all cancer cases, but patient response to therapy can vary greatly. Genetics is increasingly being recognized as a significant contributor to inter-individual response to radiation, but the biology underlying response remains poorly understood. In a study published online today in Genome Research (www.genome.org), researchers employed a pharmacogenomics approach to find biomarkers associated with radiation response that could help to more effectively tailor individual cancer treatments in the future.
Response to radiation treatment can range from complete eradication of the tumor to severe adverse reactions in normal tissues that complicate a patient's recovery. Several clinical factors, such as radiation dose and fraction, are known to influence radiation response, but it has recently been estimated that genetic factors may explain nearly 80% of the inter-individual variation of radiation response in normal tissue. If genetic variants and biological mechanisms contributing to radiation response are identified, more personalized treatment strategies could be employed in the clinic.
In this study, researchers led by Liewei Wang of the Mayo Clinic performed a genome-wide association study on 277 ethnically defined human lymphoblastoid cell lines (LCLs) to identify biomarkers for radiation response. Previous studies have found that genetic variation significantly influences gene expression following radiation treatment, however a possible relationship of basal gene expression with radiation response has not been extensively studied until now, and could be key to predicting response. The group integrated several lines of data from the LCLs, including 1.3 million single nucleotide polymorphisms (SNPs), genome-wide gene expression data, and ionizing radiation cytotoxicity phenotypes.
By looking for SNPs and gene expression patterns that associate with a radiation response phenotype, Wang's group narrowed down a list of candidate genes associated with radiation treatment response. To functionally validate the biomarkers, the team tested the associations of a set of the candidate genes in three cancer cell lines. The validation experiments confirmed the expression of five genes as involved in radiation-induced response.
Wang noted that this work not only identifies biomarkers, but also sets the stage for uncovering novel functions of these genes that could ultimately benefit individual patients. "These studies will provide a foundation for future translational studies to individualize radiation therapy based on the expression of these candidate genes," said Wang, "and may make it possible to design novel combination therapy for selected patients based on these biomarkers to overcome resistance."
Scientists from the Mayo Clinic (Rochester, MN) contributed to this study.
INFORMATION:
This work was supported by the National Institutes of Health, an ASPET-Astellas award, and a Center of Excellence in Clinical Pharmacology Award from the PhRMA Foundation.
Media contacts:
The authors are available for more information by contacting Bob Nellis, Senior Communications Consultant at the Mayo Clinic Public Affairs Office (Nellis.Robert@mayo.edu; +1-507-284-5005).
Interested reporters may obtain copies of the manuscript from Peggy Calicchia, Editorial Secretary, Genome Research (calicchi@cshl.edu; +1-516-422-4012).
About the article:
The manuscript will be published online ahead of print on October 5, 2010. Its full citation is as follows:
Niu N, Qin Y, Fridley BL, Hou J, Kalari KR, Zhu M, Wu T, Jenkins GD, Batzler A, Wang L. Radiation pharmacogenomics: A genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines. Genome Res doi:10.1101/gr.107672.110.
About Genome Research:
Launched in 1995, Genome Research (www.genome.org) is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory is a private, nonprofit institution in New York that conducts research in cancer and other life sciences and has a variety of educational programs. Its Press, originating in 1933, is the largest of the Laboratory's five education divisions and is a publisher of books, journals, and electronic media for scientists, students, and the general public.
Genome Research issues press releases to highlight significant research studies that are published in the journal.
STANFORD, Calif. — Family-based therapy, in which parents of adolescents with anorexia nervosa are enlisted to interrupt their children's disordered behaviors, is twice as effective as individual psychotherapy at producing full remission of the disease, new research from the Stanford University School of Medicine, Lucile Packard Children's Hospital and the University of Chicago shows. The study is the first head-to-head comparison of these two common treatment approaches for adolescents suffering from the eating disorder.
"This research was desperately needed," said James ...
An anorexia nervosa treatment strategy that promotes parental involvement in restoring an adolescent to healthy weight and eating habits is more effective than traditional individual-based anorexia nervosa therapy, according to new research.
The study, published online October 4 in Archives of General Psychiatry, is the first randomized clinical trial to definitively demonstrate that family based treatment, also known as the Maudsley Approach, is the treatment of choice for this patient population.
More than 50 percent of patients receiving family based treatment (FBT) ...
Re-opening a blocked heart artery isn't the only procedure that concerns doctors when they thread instruments through an opening in a thigh artery and into a heart artery. Closing up the thigh artery is also a concern.
Arteriotomy — the process of creating a hole in an "access artery" through which instruments are inserted — is the first step in procedures like angiography (to visualize blockage in the heart or neck arteries) or percutaneous coronary intervention (to re-open blocked heart arteries).
A new statement from the American Heart Association addresses the use ...
According to a consensus statement by the International Society on Hypertension in Blacks (ISHIB), high blood pressure in African-Americans is such a serious health problem that treatment should start sooner and be more aggressive. The ISHIB statement is published in Hypertension: Journal of the American Heart Association.
Complications related to high blood pressure such as stroke, heart failure and kidney damage occur much more frequently in African-Americans compared with whites.
"Evidence from several recently completed studies converged to convince our committee ...
San Diego, CA, October 5, 2010 – Influenza pandemics often come in multiple waves. As the one wave subsides, public health officials have to decide whether continuing vaccination programs is warranted to prevent or reduce a subsequent wave. In a new study published in the November issue of the American Journal of Preventive Medicine, researchers report on a new computer model that can be used to predict both subsequent-wave mechanisms and vaccination effectiveness. They conclude that additional waves in an epidemic can be mitigated by vaccination even when an epidemic appears ...
DURHAM, N.C. -- A new vaccine added to standard therapy appears to offer a survival advantage for patients suffering from glioblastoma (GBM), the most deadly form of brain cancer, according to a study from researchers at Duke University Medical Center and The University of Texas MD Anderson Cancer Center.
The vaccine also knocks out a troublesome growth factor that characterizes the most aggressive form of the disease.
"About a third of all glioblastomas are fueled by a very aggressive cancer gene, called EGFRvIII; these tumors are the 'worst of the worst,'" said John ...
Headed by the Kiel zoologist Professor Thomas Bosch, a team of scientists from Germany and Russia succeeded in deciphering the mechanisms, for the first time, with which embryos of the freshwater polyp Hydra protect themselves against bacterial colonization. The paper will be published this coming Monday (4 October 2010, press embargo 3pm US Eastern Time) in the online edition of Proceedings of the National Academy of Sciences of the United States of America (PNAS).
The researchers from Kiel University found a completely different composition of bacterial colonization ...
Children diagnosed with attention deficit/hyperactivity disorder (ADHD) at ages 4 to 6 are more likely to suffer from depression as adolescents than those who did not have ADHD at that age, according to a long-term study published in the October issue of the Archives of General Psychiatry. Although it was an uncommon occurrence, the children with ADHD also were somewhat more likely to think about or attempt suicide as adolescents.
"This study is important in demonstrating that, even during early childhood, ADHD in is seldom transient or unimportant" said study director ...
EDITOR'S NOTE: An image is available at http://www.news.wisc.edu/newsphotos/bird-biodiversity.html
— David Tenenbaum, 608-265-8549, djtenenb@wisc.edu
END ...
Babies whose mothers who receive influenza vaccines while pregnant appear less likely to be infected with flu or hospitalized for respiratory illnesses in their first six months of life, according to a report posted online today that will appear in the February 2011 print issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.
Young children are consistently at higher risk of complications from infection with the influenza virus, according to background information in the article. However, they are ineligible to be vaccinated until age ...
