1. Radiation exposure, the ATM gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study
- Author
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Bernstein, Jonine L., Halle, Robert W., Stovall, Marilyn, Boice, John D., Jr., Shore, Roy E., Langholz, Bryan, Thomas, Duncan C., Bernstein, Leslie, Lynch, Charles F., Olsen, Jorgen H., Malone, Kathleen E., Mellemkjaer, Lene, Borresen-Dale, Anne-Lise, Rosenstein, Barry S., Teraoka, Sharon N., Diep, Anh T., Smith, Susan A., Capanu, Marinela, Reiner, Anne S., Liang, Xiaolin, Gatti, Richard A., and Concannon, Patrick
- Subjects
Ionizing radiation -- Analysis ,Breast cancer -- Genetic aspects ,Breast cancer -- Care and treatment ,Breast cancer -- Diagnosis ,Breast cancer -- Development and progression ,Health - Abstract
Background Ionizing radiation is a known mutagen and an established breast carcinogen. The ATM gene is a key regulator of cellular responses to the DNA damage induced by ionizing radiation. We investigated whether genetic variants in ATM play a clinically significant role in radiation-induced contralateral breast cancer in women. Methods The Women's Environmental, Cancer, and Radiation Epidemiology Study is an international population-based case--control study nested within a cohort of 52536 survivors of unilateral breast cancer diagnosed between 1985 and 2000. The 708 case subjects were women with contralateral breast cancer, and the 1397 control subjects were women with unilateral breast cancer matched to the case subjects on age, follow-up time, registry reporting region, and race and/or ethnicity. All women were interviewed and underwent full mutation screening of the entire ATM gene. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) were estimated by using multivariable conditional logistic regression. All P values are two-sided. Results Among women who carried a rare ATM missense variant (ie, one carried by Conclusions Women who carry rare deleterious ATM missense variants and who are treated with radiation may have an elevated risk of developing contralateral breast cancer. However, the rarity of these deleterious missense variants in human populations implies that ATM mutations could account for only a small portion of second primary breast cancers. DOI: 10.1093/jnci/djq055
- Published
- 2010