ATM, radiation, and the risk of second primary breast cancer.
ATM, radiation, and the risk of second primary breast cancer.
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DOI：
10.1080/09553002.2017.1344363
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发表时间：
2017-10
影响因子：
2.6
通讯作者：
Concannon P
中科院分区：
文献类型：
--
作者：
Bernstein JL;WECARE Study Collaborative Group;Concannon P
40多年前首次提出，人类常染色体隐性遗传疾病共济失调-毛细血管扩张症（A-T）的杂合子携带者也可能增加患癌症的风险。随后的研究已经确定了负责基因，共济失调-毛细血管扩张突变（ATM），表征了A-T和各种不同癌症中该位点的遗传变异，并描述了ATM蛋白在细胞DNA损伤反应方面的功能。然而，ATM如何导致癌症风险的整体模型，特别是DNA损伤在这一过程中的作用，仍然缺乏。本综述认为这些问题的背景下，对侧乳腺癌（CBC）。ATM中A-T引起的功能缺失突变的杂合携带者患乳腺癌的风险增加。然而，对多种癌症中一系列罕见和常见的遗传变异的检查表明，ATM可能对癌症风险产生额外的影响，这种影响取决于等位基因。在CBC的情况下，在ATM的选择共同等位基因与CBC的发病率降低，而其他罕见的和预测的有害变异可能与辐射暴露共同作用，以增加风险。需要进一步研究乳腺癌中的生殖系和体细胞ATM突变的特征，并将检测到的遗传变化与功能结果（特别是辐射反应）联系起来，以全面了解ATM、辐射和乳腺癌之间的复杂关系。
It was first suggested more than 40 years ago that heterozygous carriers for the human autosomal recessive disorder Ataxia-Telangiectasia (A-T) might also be at increased risk for cancer. Subsequent studies have identified the responsible gene, Ataxia-Telangiectasia Mutated (ATM), characterized genetic variation at this locus in A-T and a variety of different cancers, and described the functions of the ATM protein with respect to cellular DNA damage responses. However, an overall model of how ATM contributes to cancer risk, and in particular, the role of DNA damage in this process, remains lacking. This review considers these questions in the context of contralateral breast cancer (CBC). Heterozygous carriers of loss of function mutations in ATM that are A-T causing, are at increased risk of breast cancer. However, examination of a range of genetic variants, both rare and common, across multiple cancers, suggests that ATM may have additional effects on cancer risk that are allele dependent. In the case of CBC, selected common alleles at ATM are associated with a reduced incidence of CBC, while other rare and predicted deleterious variants may act jointly with radiation exposure to increase risk. Further studies that characterize germline and somatic ATM mutations in breast cancer and relate the detected genetic changes to functional outcomes, particularly with regard to radiation responses, are needed to gain a complete picture of the complex relationship between ATM, radiation and breast cancer.
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影响因子：
3.9
作者：
Claus, EB;Stowe, M;Holford, T
通讯作者：
Holford, T
DOI：
10.1083/jcb.201204035
发表时间：
2012-08-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Daniel JA;Pellegrini M;Lee BS;Guo Z;Filsuf D;Belkina NV;You Z;Paull TT;Sleckman BP;Feigenbaum L;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
13.8
作者：
Bosotti, R;Isacchi, A;Sonnhammer, ELL
通讯作者：
Sonnhammer, ELL
DOI：
10.1093/jnci/djq055
发表时间：
2010-04-07
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Bernstein, Jonine L.;Haile, Robert W.;Concannon, Patrick
通讯作者：
Concannon, Patrick
影响因子：
64.8
作者：
GATTI, RA;BERKEL, I;YODER, F
通讯作者：
YODER, F