Year: 2008
Type: article
Study design: Observational Study
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.
Source: Cancer Research
Authors: Patrick Concannon, Robert W. Haile, Anne-Lise Børresen-Dale, Barry S. Rosenstein, Richard A. Gatti, Sharon N. Teraoka, Anh T. Diep, Laila Jansen, David P. Atencio, Bryan Langholz, Marinela Capanu, Xiaolin Liang, Colin B. Begg, Duncan C. Thomas, Leslie Bernstein, Jørgen H. Olsen, Kathleen E. Malone, Charles F. Lynch, Hoda Anton-Culver, Jonine L. Bernstein, for the Women's Environment, Cancer, and Radiation Epidemiology Study Collaborative Group
Institutions: University of Virginia, University of Southern California, University of Oslo, Icahn School of Medicine at Mount Sinai, University of California, Los Angeles, Memorial Sloan Kettering Cancer Center, City Of Hope National Medical Center, Danish Cancer Society, Fred Hutch Cancer Center, University of Iowa, University of California, Irvine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: Epidemiologic Parameters of Rare Cancer Risk Factors, Isolation of genes for radiation sensitivity, G3200667085, Interaction of Radiation, BRCA1/2, and Breast Cancer, G4671016071, ATM mutations in breast cancer - a functional approach, BREAST CANCER, RADIATION EXPOSURE, AND THE ATM GENE, G6380010387, G6483386616, Estimating Cancer Risks of Rare Genetic Variants, Genome-Wide Association Study of Radiation Exposure and Bilateral Breast Cancer, Cancer Center Support Grant
OpenAlex ID: W2010761537