ATM, radiation, and the risk of second primary breast cancer Journal Article

Authors: Bernstein, J. L.; WECARE Study Collaborative Group; Concannon, P.
Contributors: Capanu, M.; Liang, X.; Orlow, I.; Reiner, A. S.; Robson, M.; Woods, M.
Article Title: ATM, radiation, and the risk of second primary breast cancer
Abstract: PURPOSE: 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 regard 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). CONCLUSIONS: 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.
Keywords: genetics; mutation; animal; animals; genetic predisposition to disease; breast cancer; breast neoplasms; neoplasms, radiation-induced; atm protein; radiation therapy; neoplasms, second primary; genetic predisposition; atm; ataxia-telangiectasia; radiation induced neoplasm; allelic heterogeneity; humans; human; ataxia telangiectasia mutated proteins
Journal Title: International Journal of Radiation Biology
Volume: 93
Issue: 10
ISSN: 0955-3002
Publisher: Taylor & Francis Group Ltd.  
Date Published: 2017-01-01
Start Page: 1121
End Page: 1127
Language: English
DOI: 10.1080/09553002.2017.1344363
PUBMED: 28627265
PROVIDER: scopus
PMCID: PMC6113688
Notes: Review -- Export Date: 2 November 2017 -- Source: Scopus
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MSK Authors
  1. Anne S Reiner
    122 Reiner
  2. Mark E Robson
    368 Robson
  3. Irene Orlow
    192 Orlow
  4. Marinela Capanu
    211 Capanu
  5. Jonine L Bernstein
    104 Bernstein
  6. Xiaolin Liang
    41 Liang
  7. Meghan   Woods
    13 Woods