Genetic Variations May Affect Radiation Sensitivity

Originally Published MDDI December 2003

R&D DIGEST

Erin Bradford

Specific variations in the basic building blocks of DNA may affect a patient's sensitivity to radiotherapy. Researchers in Denmark suggest that it might be possible to develop gene-based, predictive tests to enable doctors to determine the highest dose of radiation a patient could tolerate, thereby improving the efficacy of radiotherapy treatment.

During this year's European Cancer Conference, Nicolaj Andreassen, MD, research fellow in the department of experimental clinical oncology at the University of Aarhus (Aarhus, Denmark), described an analysis that studied variations in five genes known to be involved in the body's response to radiation treatment. He and his colleagues looked at the sequence of the four nucleotides that make up the DNA of each gene, and identified places where the sequence varied from the norm. These variations could influence the amount of radiation a patient can handle, the researchers suggested.

The places on the genes where the variations are found are called single nucleotide polymorphisms (SNPs). SNPs represent sites where a nucleotide varies from the nucleotide that most people have. The occurrence of SNPs means that certain people may have a protein that works differently than the corresponding protein would in a person with a normal nucleotide sequence.

“Our findings indicate that normal tissue radiosensitivity should be regarded as a trait dependent on the combined effect of variation in several genes, and the SNPs could constitute a substantial proportion of such genetic determinants. This means that normal tissue radiosensitivity could potentially be predicted from individual genetic patterns or profiles,” Andreassen explains.

Although the results need confirmation and more work is necessary, Andreassen thinks this discovery could be the first step to developing tests to predict the way individual patients would respond to radiotherapy. “If normal tissue radiosensitivity could be reliably predicted prior to treatment, the radioresistant patients could possibly be offered a higher dose. In many cases, this would increase the chances of cure substantially,” he adds.

At present, radiotherapy doses are often restricted by what the most radiosensitive patients can tolerate. The doses keep the risk of severe normal tissue damage below 5–10%, despite the fact that many patients might be able to tolerate a larger dose without severe tissue reactions.

Andreassen says that, at this stage, it is difficult to predict the implications this study will have for radiation device manufacturers. “The ultimate aim of our research is to establish a gene-based assay that could be used routinely to predict the normal tissue outcome from radiotherapy,” he said. 

Yet he predicts that the years to come will bring an increasing integration between molecular diagnostics and clinical decision making. Until that time, radiation device manufacturers are advised to keep an eye on research such as Andreassen's.

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