Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy
Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy
复制标题
DOI：
10.1007/s000660050005
复制
发表时间：
2000-05-01
影响因子：
3.1
通讯作者：
Scott, D
中科院分区：
文献类型：
--
作者：
Scott, D
目的：本文简要总结了英国曼彻斯特帕特森癌症研究所癌症遗传学系在过去6年中对这一主题的研究。患有隐性遗传性疾病共济失调-毛细血管扩张症（A-T）的患者具有癌症倾向，并且在放射治疗后发生严重反应，他们也具有高度放射敏感性细胞，特别是当染色体损伤被用作放射敏感性的量度时。增强的染色体放射敏感性也是许多其他癌症易感性疾病的特征。我们研究了这种放射敏感性作为癌症易感性和对放射治疗反应的标志物在一般population.Results中的可能作用：我们发现，42%（57/135）的乳腺癌患者表现出染色体放射敏感性时，淋巴细胞在G（2）期的细胞周期，相比之下，6%（6/105）的健康对照（图1）。这些数字远高于乳腺癌患者（< 5%）和对照组（0.5%）中共济失调-毛细血管扩张症基因（杂合子）携带者的估计频率。我们还通过研究乳腺癌病例的亲属获得了G（2）敏感性遗传性的证据（图2和图3）。遗传模式相对简单，可归因于每个家族中1或2个基因分离（图4）。在一项前瞻性研究中，123例乳腺癌患者中，9例（7%）对放射治疗有严重急性反应，其平均G（2）敏感性显著高于其余患者（p = 0.001）（图5）。在16例急性不良反应患者中，我们没有发现共济失调-毛细血管扩张症基因（ATM）突变。使用另一种染色体检测（G（u）淋巴细胞微核诱导），我们发现，严重晚期反应患者的平均放射敏感性高于正常反应者。例如，8例7例纤维化患者比39例正常反应患者更敏感（p = 0.055）（图4）。然而，这些染色体检测的歧视权力是太低，他们单独使用在临床setting.Conclusion：我们的研究结果提供了很好的证据，基因以外的ATM，赋予染色体放射敏感性，参与了低转移率易感性乳腺癌的高比例的情况下，并有助于放疗后的不良反应。
Aim: This paper briefly summarizes the research on this topic, undertaken in the Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, England, over the previous 6 years.Patients and Method: Patients with the recessively-inherited disease, ataxia-telangiectasia (A-T), who are cancer-prone and suffer severe reactions after radiotherapy, also have highly radiosensitive cells, particularly when chromosome damage is used as the measure of radiosensitivity. Enhanced chromosomal radiosensitivity is also a feature of many other cancer-prone disorders. We have investigated the possible role of such radiosensitivity as a marker of cancer predisposition and response to radiotherapy in the general population.Results: We found that 42% (57/135) of breast cancer patients exhibit chromosomal radiosensitivity when lymphocytes are irradiated in the G(2) phase of the cell cycle, compared with 6% (6/105) of healthy controls (Figure 1). These figures are much higher than the estimated frequencies of carriers of the ataxia-telangiectasia gene (heterozygotes) amongst breast cancer patients (< 5%) and controls (0.5%). We have also obtained evidence of heritability of G(2) sensitivity by studying relatives of breast cancer cases (Figures 2 and 3). The pattern of inheritance is relatively simple and attributable to 1 or 2 genes segregating in each family (Figure 4).In a prospective: study of 123 breast cancer patients, 9 (7%) had severe acute reactions to radiotherapy and their mean G(2) sensitivity was significantly greater (p = 0.001) than that of the remaining patients (Figure 5). In 16 patients with adverse acute reactions we found no mutations of the ataxia-telangiectasia gene (ATM). Using another chromosomal assay (micronucleus induction in G(u) lymphocytes) we found that the mean radiosensitivity of patients with severe late reactions was higher than that of normal reactors. For example, 8 patients with seven fibrosis were more sensitive (p = 0.055) than 39 patients with a normal response (Figure 4). However, the discriminatory power of these chromosomal assays is too low for them to bt used alone in a clinical setting.Conclusion: Our results provide good evidence that genes other than ATM, that confer chromosomal radiosensitivity, are involved in low penetrance predisposition to breast cancer in a high proportion of cases and contribute to adverse reactions after radiotherapy.