PT  - JOURNAL ARTICLE
AU  - Concannon, Patrick
AU  - Haile, Robert W.
AU  - Børresen-Dale, Anne-Lise
AU  - Rosenstein, Barry S.
AU  - Gatti, Richard A.
AU  - Teraoka, Sharon N.
AU  - Diep, Anh T.
AU  - Jansen, Laila
AU  - Atencio, David P.
AU  - Langholz, Bryan
AU  - Capanu, Marinela
AU  - Liang, Xiaolin
AU  - Begg, Colin B.
AU  - Thomas, Duncan C.
AU  - Bernstein, Leslie
AU  - Olsen, Jørgen H.
AU  - Malone, Kathleen E.
AU  - Lynch, Charles F.
AU  - Anton-Culver, Hoda
AU  - Bernstein, Jonine L.
ED  - , 
TI  - Variants in the ATM Gene Associated with a Reduced Risk of Contralateral Breast Cancer
AID  - 10.1158/0008-5472.CAN-08-0134
DP  - 2008 Aug 15
TA  - Cancer Research
PG  - 6486--6491
VI  - 68
IP  - 16
4099  - http://cancerres.aacrjournals.org/content/68/16/6486.short
4100  - http://cancerres.aacrjournals.org/content/68/16/6486.full
SO  - Cancer Res2008 Aug 15; 68
AB  - 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. [Cancer Res 2008;68(16):6486–91] ©2008 American Association for Cancer Research.