The ATM gene and breast cancer:: is it really a risk factor?
The ATM gene and breast cancer:: is it really a risk factor?
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DOI：
10.1016/s1383-5742(00)00034-x
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发表时间：
2000-04-01
影响因子：
5.3
通讯作者：
Hall, J
中科院分区：
文献类型：
--
作者：
Angèle, S;Hall, J
大多数乳腺癌病例的遗传决定因素仍然难以捉摸。虽然BRCA 1 '和BRCA 2突变显著增加了家族性乳腺癌风险，但它们对散发性乳腺癌的影响很小。在一般人群中，此类病例的基因常发生改变，如共济失调性毛细血管扩张症（AT）中的基因突变，ATM可能是重要的危险因素。最初的兴趣在研究ATM杂合子在乳腺癌中产生的AT家族的流行病学研究结果，其中AT杂合子妇女有乳腺癌的风险增加，估计有1%的人口是AT杂合子。AT患者的临床特征之一是细胞对电离辐射的极端敏感性。这一观察结果，连同发现，一个显着比例的乳腺癌患者表现出夸张的急性或晚期正常组织反应放疗后，导致建议，AT杂合性在放射敏感性和乳腺癌的发展中发挥作用。在11号染色体上ATM基因区域的杂合性丢失，已发现在约40%的散发性乳腺肿瘤。然而，在散发性乳腺癌病例中筛查ATM突变，显示或不显示对放射治疗的不良影响，并没有显示ATM基因参与的程度。它们的大小和使用蛋白质截短测试来识别突变限制了许多这些研究。后一个参数是关键的，因为AT患者中的突变谱可能不代表其他疾病中的ATM突变。ATM基因中罕见序列变异的潜在作用，有时被报告为多态性，也需要在较大的乳腺癌患者和对照组中进行充分评估，以确定它们是否代表癌症和/或辐射敏感性易感突变。(C)2000年，爱思唯尔科学公司（Elsevier Science B. V.），所有的灯都被怨恨了。
The genetic determinants for most breast cancer cases remain elusive. Whilst mutations in BRCA1' and BRCA2 significantly contribute to familial breast cancer risk, their contribution to sporadic breast cancer is low. Zn such cases genes frequently altered in the general population, such as the gene mutated in Ataxia telangiectasia(AT), ATM may be important risk factors. The initial interest in studying ATM heterozygosity in breast cancer arose from the findings of epidemiological studies of AT families in which AT heterozygote women had an increased risk of breast cancer and estimations that 1% of the population are AT heterozygotes. One of the clinical features of AT patients is extreme cellular sensitivity to ionising radiation. This observation, together with the finding that a significant proportion of breast cancer patients show an exaggerated acute or late normal tissue reactions after radiotherapy, has lead to the suggestion that AT heterozygosity plays a role in radiosensitivity and breast cancer development. Loss of heterozygosity in the region of the ATM gene on chromosome 11, has been found in about 40% of sporadic breast tumours. However, screening for ATM mutations in sporadic breast cancer cases, showing or not adverse effects to radiotherapy, has not revealed the magnitude of involvement of the ATM gene expected. Their size and the use of the protein truncation test to identify mutations limit many of these studies. This latter parameter is critical as the profile of mutations in AT patients may not be representative of the ATM mutations in other diseases. The potential role of rare sequence variants within the ATM gene, sometimes reported as polymorphisms, also needs to be fully assessed in larger cohorts of breast cancer patients and controls in order to determine whether they represent cancer and/or radiation sensitivity predisposing mutations. (C) 2000 Elsevier Science B.V. All lights resented.