Biomarkers Identified for Personalizing Radiation Cancer Treatment

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 interindividual response to radiation, but the biology underlying response remains poorly understood. In a study, researchers utilized a pharmacogenomics strategy to find biomarkers associated with radiation response that could help to customize more effectively individual cancer treatments.

Response to radiation treatment can vary 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 clarify nearly 80% of the inter-individual variation of radiation response in normal tissue. If genetic variants and biologic processes contributing to radiation response are identified, more personalized treatment approaches could be employed in the clinic.

In this study, researchers led by Dr. Liewei Wang of the Mayo Clinic (Rochester, MN, USA), performed a genome-wide association study on 277 ethnically defined human lymphoblastoid cell lines (LCLs) to identify biomarkers for radiation response. Earlier studies have found that genetic variation considerably influences gene expression following radiation treatment; however, a possible relationship of basal gene expression with radiation response has not been extensively evaluated until now, and could be critical to predicting response. The group incorporated 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, Dr. Wang's team narrowed down a list of candidate genes associated with radiation treatment response. To validate the biomarkers functionally, the team assessed 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.

Dr. 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,” concluded Dr. Wang, "and may make it possible to design novel combination therapy for selected patients based on these biomarkers to overcome resistance.”

The study's findings were published online October 5, 2010, in the journal Genome Research.

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