TY - JOUR
T1 - A preliminary report
T2 - Frequency of A-T heterozygotes among prostate cancer patients with severe late responses to radiation therapy
AU - Hall, Eric J.
AU - Schiff, Peter B.
AU - Hanks, Gerald E.
AU - Brenner, David J.
AU - Russo, James
AU - Chen, Jing
AU - Sawant, Satin G.
AU - Pandita, Tej K.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - PURPOSE: To investigate whether a significant proportion of prostate 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 ATM 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 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.
AB - PURPOSE: To investigate whether a significant proportion of prostate 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 ATM 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 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.
KW - A-T heterozygotes
KW - Ataxia-telangientasia
KW - Genetic predisposition
KW - Late effects
KW - Mutations in ATM gene
KW - Prostate cancer
KW - Radiation therapy and cancer
KW - Radiosensitive subgroup
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M3 - Article
C2 - 9853138
AN - SCOPUS:0031738103
VL - 4
SP - 385
EP - 389
JO - Cancer Journal from Scientific American
JF - Cancer Journal from Scientific American
SN - 1081-4442
IS - 6
ER -