Journal article
Variants in the ATM gene associated with a reduced risk of contralateral breast cancer
Cancer research (Chicago, Ill.), Vol.68(16), pp.6486-6491
08/15/2008
DOI: 10.1158/0008-5472.CAN-08-0134
PMCID: PMC2562548
PMID: 18701470
Abstract
Between 5% and 10% of women who survive a first primary breast cancer will subsequently develop a second primary cancer in the contralateral breast. The Women's Environment, Cancer, and Radiation Epidemiology Study was designed to identify genetic and environmental determinants of contralateral breast cancer (CBC). In this study, 708 women with asynchronous CBC served as cases and 1,397 women with unilateral breast cancer served as controls. ATM, a serine-threonine kinase, controls the cellular response to DNA double-strand breaks, and has been implicated in breast cancer risk. Complete mutation screening of the ATM gene in all 2,105 study participants identified 240 distinct sequence variants; only 15 were observed in >1% of subjects. Among the rare variants, deleterious alleles resulting in loss of ATM function were associated with a nonsignificant increase in risk of CBC. In contrast, carriers of common variants had a statistically significant reduction in risk of CBC. Four of these 15 variants were individually associated with a significantly decreased risk of second primary breast cancer [c.1899-55T>G, rate ratio (RR), 0.5; 95% confidence interval (CI), 0.3-0.8; c.3161C>G, RR, 0.5; 95% CI, 0.3-0.9; c.5558A>T, RR, 0.2; 95% CI, 0.1-0.6; c.6348-54T>C RR, 0.2; 95% CI, 0.1-0.8]. These data suggest that some alleles of ATM may exert an antineoplastic effect, perhaps by altering the activity of ATM as an initiator of DNA damage responses or a regulator of p53.
Details
- Title: Subtitle
- Variants in the ATM gene associated with a reduced risk of contralateral breast cancer
- Creators
- Patrick Concannon - Department of Biochemistry and Molecular Genetics and Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22908-0733, USA. patcon@virginia.eduRobert W HaileAnne-Lise Børresen-DaleBarry S RosensteinRichard A GattiSharon N TeraokaT Anh DiepLaila JansenDavid P AtencioBryan LangholzMarinela CapanuXiaolin LiangColin B BeggDuncan C ThomasLeslie BernsteinJørgen H OlsenKathleen E MaloneCharles F LynchHoda Anton-CulverJonine L BernsteinWomen's Environment, Cancer, and Radiation Epidemiology Study Collaborative Group
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.68(16), pp.6486-6491
- Publisher
- United States
- DOI
- 10.1158/0008-5472.CAN-08-0134
- PMID
- 18701470
- PMCID
- PMC2562548
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Grant note
- R01 CA129639 / NCI NIH HHS CA83178 / NCI NIH HHS U01 CA083178-01 / NCI NIH HHS R01 CA057569 / NCI NIH HHS U01 CA083178-03 / NCI NIH HHS U01 CA083178 / NCI NIH HHS U01 CA083178-05 / NCI NIH HHS CA097397 / NCI NIH HHS R01 CA098438-03 / NCI NIH HHS P30 CA008748 / NCI NIH HHS CA098438 / NCI NIH HHS U01 CA083178-02 / NCI NIH HHS U01 CA083178-04 / NCI NIH HHS R01 CA112450-03 / NCI NIH HHS R01 CA057569-16 / NCI NIH HHS R01 CA112450 / NCI NIH HHS R01 CA098438 / NCI NIH HHS U01 CA083178-06 / NCI NIH HHS R01 CA097397 / NCI NIH HHS R01 CA097397-05 / NCI NIH HHS CA112450 / NCI NIH HHS R01 CA131010 / NCI NIH HHS
- Language
- English
- Date published
- 08/15/2008
- Academic Unit
- Epidemiology
- Record Identifier
- 9983996080202771
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