ATM sequence variants are predictive of adverse radiotherapy response among patients treated for prostate cancer

被引:70
作者
Cesaretti, JA
Stock, RG
Lehrer, S
Atencio, DA
Bernstein, JL
Stone, NN
Wallenstein, S
Green, S
Loeb, K
Kollmeier, M
Smith, M
Rosenstein, BS
机构
[1] Mt Sinai Sch Med, Dept Radiat Oncol, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA
[3] Mt Sinai Sch Med, Dept Urol, New York, NY 10029 USA
[4] Mt Sinai Sch Med, Dept Biomath Sci, New York, NY 10029 USA
[5] NYU, Sch Med, Dept Radiat Oncol, New York, NY USA
[6] Vet Affairs Med Ctr, Bronx, NY USA
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2005年 / 61卷 / 01期
关键词
ATM gene; radiation sensitivity; DHPLC; prostate cancer; brachytherapy;
D O I
10.1016/j.ijrobp.2004.09.031
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To examine whether the presence of sequence variants in the ATM (mutated in ataxia-telangiectasia) gene is predictive for the development of radiation-induced adverse responses resulting from I-125 prostate brachytherapy for early-stage prostate cancer. Materials and Methods: Thirty-seven patients with a minimum of 1-year follow-up who underwent I-125 prostate brachytherapy of early-stage prostate cancer were screened for DNA sequence variations in all 62 coding exons of the ATM gene using denaturing high-performance liquid chromatography. The clinical course and postimplant dosimetry for each genetically characterized patient were obtained from a database of 2,020 patients implanted at Mount Sinai Hospital after 1990. Results: Twenty-one ATM sequence alterations located within exons, or in short intronic regions flanking each exon, were found in 16 of the 37 patients screened. For this group, 10 of 16 (63%) exhibited at least one form of adverse response. In contrast, of the 21 patients who did not harbor an ATM sequence variation, only 3 of 21 (14%) manifested radiation-induced adverse responses (p = 0.005). Nine of the patients with sequence alterations specifically possessed missense mutations, which encode for amino acid substitutions and are therefore more likely to possess functional importance. For this group, 7 of 9 (78%) exhibited at least one form of adverse response. In contrast, of the 28 patients who did not have a missense alteration, only 6 of 28 (21%) manifested any form of adverse response to the radiotherapy (p = 0.004). Of the patients with missense variants, 5 of 9 (56%) exhibited late rectal bleeding vs. 1 of 28 (4%) without such alterations (p = 0.002). Of those patients who were at risk for developing erectile dysfunction, 5 of 8 (63%) patients with missense mutations developed prospectively evaluated erectile dysfunction as opposed to 2 of 20 (10%) without these sequence alterations (p = 0.009). Conclusions : Possession of sequence variants in the ATM gene, particularly those that encode for an amino acid substitution, is predictive for the development of adverse radiotherapy responses among patients treated with I-125 prostate brachytherapy. (C) 2005 Elsevier Inc.
引用
收藏
页码:196 / 202
页数:7
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