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Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6635-40. Epub 2004 Apr 19.

Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage.

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1
Department of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P = 2.2 x 10(-7)). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.

PMID:
15096622
PMCID:
PMC404097
DOI:
10.1073/pnas.0307761101
[Indexed for MEDLINE]
Free PMC Article
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