Possession of ATM Sequence Variants as Predictor for Late Normal Tissue Responses in Breast Cancer Patients Treated With Radiotherapy
- Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States)
- Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)
- Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, NJ (United States)
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Purpose: The ATM gene product is a central component of cell cycle regulation and genomic surveillance. We hypothesized that DNA sequence alterations in ATM predict for adverse effects after external beam radiotherapy for early breast cancer. Methods and Materials: A total of 131 patients with a minimum of 2 years follow-up who had undergone breast-conserving surgery and adjuvant radiotherapy were screened for sequence alterations in ATM using DNA from blood lymphocytes. Genetic variants were identified using denaturing high performance liquid chromatography. The Radiation Therapy Oncology Group late morbidity scoring schemes for skin and subcutaneous tissues were applied to quantify the radiation-induced effects. Results: Of the 131 patients, 51 possessed ATM sequence alterations located within exons or in short intron regions flanking each exon that encompass putative splice site regions. Of these 51 patients, 21 (41%) exhibited a minimum of a Grade 2 late radiation response. In contrast, of the 80 patients without an ATM sequence variation, only 18 (23%) had radiation-induced adverse responses, for an odds ratio of 2.4 (95% confidence interval, 1.1-5.2). Fifteen patients were heterozygous for the G{yields}A polymorphism at nucleotide 5557, which causes substitution of asparagine for aspartic acid at position 1853 of the ATM protein. Of these 15 patients, 8 (53%) exhibited a Grade 2-4 late response compared with 31 (27%) of the 116 patients without this alteration, for an odds ratio of 3.1 (95% confidence interval, 1.1-9.4). Conclusion: Sequence variants located in the ATM gene, in particular the 5557 G{yields}A polymorphism, may predict for late adverse radiation responses in breast cancer patients.
- OSTI ID:
- 21039568
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 69, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2007.04.012; PII: S0360-3016(07)00671-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
Similar Records
Common Variants of GSTP1, GSTA1, and TGF{beta}1 are Associated With the Risk of Radiation-Induced Fibrosis in Breast Cancer Patients
Haplotype-Based Analysis of Genes Associated With Risk of Adverse Skin Reactions After Radiotherapy in Breast Cancer Patients