Germline glutathione S-transferase variants in breast cancer: Relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy
- Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo (Norway) and Medical Faculty, University of Oslo, Oslo (Norway)
- Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo (Norway)
- Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Oslo (Norway)
- Medical Faculty, University of Oslo, Oslo (Norway)
Purpose: To explore whether certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of breast cancer or the level of radiation-induced adverse effects after two fractionation patterns of adjuvant radiotherapy. Methods and Materials: The prevalence of germline polymorphic variants in GSTM1, GSTP1, and GSTT1 was determined in 272 breast cancer patients and compared with that in a control group of 270 women from the general population with no known history of breast cancer. The genetic variants were determined using multiplex polymerase chain reaction followed by restriction enzyme fragment analysis. In 253 of the patients surveyed for radiotherapy-induced side effects after a median observation time of 13.7 years (range, 7-22.8 years), the genotypes were related to the long-term effects observed after two fractionation patterns (treatment A, 4.3 Gy in 10 fractions for 156 patients; and treatment B, 2.5 Gy in 20 fractions for 97; both administered within a 5-week period). Results: None of the GST polymorphisms conferred an increased risk of breast cancer, either alone or in combination. Compared with treatment B, treatment A was followed by an increased level of moderate to severe radiation-induced side effects for all the endpoints studied (i.e., degree of telangiectasia, subcutaneous fibrosis and atrophy, lung fibrosis, costal fractures, and pleural thickening; p <0.001 for all endpoints). A significant association was found between the level of pleural thickening and the GSTP1 Ile105Val variant. Conclusion: The results of this study have illustrated the impact of hypofractionation on the level of adverse effects and indicated that the specific alleles of GSTP1, M1, and T1 studied here may be significant in determining the level of adverse effects after radiotherapy.
- OSTI ID:
- 20944776
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 67, Issue 4; Other Information: DOI: 10.1016/j.ijrobp.2006.11.009; PII: S0360-3016(06)03378-5; 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
SNP in TXNRD2 Associated With Radiation-Induced Fibrosis: A Study of Genetic Variation in Reactive Oxygen Species Metabolism and Signaling
Common Variants of GSTP1, GSTA1, and TGF{beta}1 are Associated With the Risk of Radiation-Induced Fibrosis in Breast Cancer Patients