Journal article
ATM, radiation, and the risk of second primary breast cancer
International journal of radiation biology, Vol.93(10), pp.1121-1127
10/01/2017
DOI: 10.1080/09553002.2017.1344363
PMCID: PMC6113688
PMID: 28627265
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.
Details
- Title: Subtitle
- ATM, radiation, and the risk of second primary breast cancer
- Creators
- Jonine L. Bernstein - Memorial Sloan Kettering Cancer CenterPatrick Concannon - University of FloridaWomen’s Environmental, Cancer, And Radiation Epidemiology (WECARE) Study Collaborative Group (Institution)
- Contributors
- Michele West (Contributor) - University of Iowa, Epidemiology
- Resource Type
- Journal article
- Publication Details
- International journal of radiation biology, Vol.93(10), pp.1121-1127
- DOI
- 10.1080/09553002.2017.1344363
- PMID
- 28627265
- PMCID
- PMC6113688
- NLM abbreviation
- Int J Radiat Biol
- ISSN
- 0955-3002
- eISSN
- 1362-3095
- Publisher
- Taylor & Francis
- Number of pages
- 7
- Grant note
- U01 CA83178; R01 CA97397; R01 CA129639; R01 CA114236; P30 CA008748 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA114236 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 1-16-1-0048 / Defense Threat Reduction Agency; United States Department of Defense R01ES027121 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01 ES027121 / NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Language
- English
- Date published
- 10/01/2017
- Academic Unit
- Epidemiology
- Record Identifier
- 9984368208002771
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