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Hall EJ , Schiff PB , Hanks GE , Brenner DJ , Russo J , Chen J , Sawant SG , Pandita TK
A preliminary report: Frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy
Cancer Journal from Scientific American. 1998 Nov-Dec;4(6) :385-389
PMID: ISI:000077291800010   
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PURPOSE To investigate whether a significant proportion of pros tate cancer patients who have late sequelae after high-dose external-beam conformal radiation therapy are radiosensitive because they are carriers of ataxia-telangiectasia, that is, are heterozygous for mutations in the ATM gene. PATIENTS AND METHODS A group of prostate cancer patients were selected who experienced severe late sequelae, specifically proctitis or cystitis, after high-dose external-beam conformal radiation therapy, together with a control group of patients treated in the same way but who did not have severe late effects. Blood samples were taken from these patients, genomic DNA extracted, and mutations sought in the A TM gene. RESULTS Of 17 late- effect patients in whom most or all of the ATM gene has been examined, significant mutations (17.6%) were identified in three. No significant mutations were found in the control group. The incidence of ataxia- telangiectasia heterozygotes in the United States population is 1% to 2%. DISCUSSION These preliminary data suggest that a disproportionate number, but by no means all, of prostate cancer radiotherapy patients who experience severe late effects are ataxia-telangiectasia heterozygotes. If this conclusion is confirmed, these individuals could be: identified prospectively and, with dose de-escalation, spared a great deal of discomfort and suffering. As a corollary, if most of the small late-effects population were prospectively identifiable, the dose to the remaining population could potentially be escalated. Present methods of identifying mutations;ions in a large gene, such as ATM, are cumbersome and expensive, but the technology is evolving rapidly, so that rapid screening of the ATM gene is imminent.
Times Cited: 13 English Article 144AZ CANCER J SCI AM