Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors:: Association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes
Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors:: Association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes
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DOI：
10.1016/j.ijrobp.2004.12.027
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发表时间：
2005-07-15
影响因子：
7
通讯作者：
Thierens, H
中科院分区：
文献类型：
--
作者：
De Ruyck, K;Van Eijkeren, M;Thierens, H
目的：检查 XRCCI (194Arg/Trp、280Arg/His、399Arg/Gln、632Gln/Gln)、XRCC3 (5' UTR 4.541A > G、IVS5-14 17.893A > G、241Thr/Met) 和 OGG1 中多态性的关联(326Ser/Cys)随着晚期放疗的发展 (RT) 反应并评估体外染色体放射敏感性与临床放射敏感性之间的相关性。方法和材料：本研究纳入了 62 名接受 RT 治疗的宫颈癌或子宫内膜癌女性。根据不良事件通用术语标准 3.0 版量表，22 名患者出现了晚期不良 RT 反应。采用聚合酶链反应-限制性片段长度多态性 (PCR-RFLP) 检测来检查多态性位点，使用 G2 检测来测量染色体放射敏感性，并使用精算方法对患者组进行比较。 结果：XRCC3 IVS5-14 多态性等位基因与发生晚期 RT 反应的风险显着相关（比值比 3.98，p = 0.025），XRCCI 密码子 194 变体显示出显着的保护作用（p = 0.028）。 XRCCI 和 XRCC3 中具有三个或更多风险等位基因的患者发生正常组织反应的风险显着增加（比值比 10.10，p = 0.001）。有正常组织反应的患者中每个细胞的平均染色单体断裂数明显多于没有反应的患者（分别为 1.16 和 1.34；p = 0.002）。高染色体放射敏感性患者的年并发症风险比中等染色体放射敏感性患者高 9.2 倍。将 G2 分析与风险等位基因模型相结合，我们能够识别出 23% 的晚期正常组织反应患者，且没有假阳性结果。 结论：本研究的结果表明，临床放射敏感性与 G2 染色体放射敏感性增强相关，并且与 DNA 修复基因中不同多态性的组合显着相关。 (c) 2005 年爱思唯尔公司。
Purpose: To examine the association of polymorphisms in XRCCI (194Arg/Trp, 280Arg/His, 399Arg/Gln, 632Gln/Gln), XRCC3 (5' UTR 4.541A > G, IVS5-14 17.893A > G, 241Thr/Met), and OGG1 (326Ser/Cys) with the development of late radiotherapy (RT) reactions and to assess the correlation between in vitro chromosomal radiosensitivity and clinical radiosensitivity.Methods and Materials: Sixty-two women with cervical or endometrial cancer treated with RT were included in the study. According to the Common Terminology Criteria for Adverse Events, version 3.0, scale, 22 patients showed late adverse RT reactions. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were performed to examine polymorphic sites, the G2 assay was used to measure chromosomal radiosensitivity, and patient groups were compared using actuarial methods.Results: The XRCC3 IVS5-14 polymorphic allele was significantly associated with the risk of developing late RT reactions (odds ratio 3.98, p = 0.025), and the XRCCI codon 194 variant showed a significant protective effect (p = 0.028). Patients with three or more risk alleles in XRCCI and XRCC3 had a significantly increased risk of developing normal tissue reactions (odds ratio 10.10,p = 0.001). The mean number of chromatid breaks per cell was significantly greater in patients with normal tissue reactions than in patients with no reactions (1.16 and 1.34, respectively; p = 0.002). Patients with high chromosomal radiosensitivity showed a 9.2-fold greater annual risk of complications than patients with intermediate chromosomal radiosensitivity. Combining the G2 analysis with the risk allele model allowed us to identify 23% of the patients with late normal tissue reactions, without false-positive results.Conclusion: The results of the present study showed that clinical radiosensitivity is associated with an enhanced G2 chromosomal radiosensitivity and is significantly associated with a combination of different polymorphisms in DNA repair genes. (c) 2005 Elsevier Inc.