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. 2006;8(4):R40.
doi: 10.1186/bcr1526.

Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study

Christine B Ambrosone  1 , Chunqiao Tian, Jiyoung Ahn, Silke Kropp, Irmgard Helmbold, Dietrich von Fournier, Wulf Haase, Marie Luise Sautter-Bihl, Frederik Wenz, Jenny Chang-Claude
Affiliations

Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study

Christine B Ambrosone et al. Breast Cancer Res. 2006.

Abstract

Introduction: The cytotoxic effects of radiation therapy are mediated primarily through increased formation of hydroxyl radicals and reactive oxygen species, which can damage cells, proteins and DNA; the glutathione S-transferases (GSTs) function to protect against oxidative stress. We hypothesized that polymorphisms encoding reduced or absent activity in the GSTs might result in greater risk for radiation-associated toxicity.

Methods: Women receiving therapy in radiation units in Germany following lumpectomy for breast cancer (1998-2001) provided a blood sample and completed an epidemiological questionnaire (n = 446). Genotypes were determined using Sequonom MALDI-TOF (GSTA1, GSTP1) and Masscode (GSTM1, GSTT1). Biologically effective radiotherapy dose (BED) was calculated, accounting for differences in fractionation and overall treatment time. Side effects considered were grade 2c and above, as classified using the modified Common Toxicity Criteria. Predictors of toxicity were modelled using Cox regression models in relation to BED, with adjustment for treating clinic, photon field, beam energy and boost method, and potential confounding variables.

Results: Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04-4.99). No associations were noted for the other GST genotypes.

Conclusion: These data indicate that GSTP1 plays an important role in protecting normal cells from damage associated with radiation therapy. Studies examining the effects of GSTP1 polymorphisms on toxicity, recurrence and survival will further inform individualized therapeutics based on genotypes.

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Figures

Figure 1
Figure 1
Probability of toxicity-free effects. Kaplan-Meier curve for the probability of toxicity-free effects (without Common Toxicity Criteria grade 2c toxicity or greater) by GSTP1 genotypes.
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References

    1. Fisher B, Bauer M, Margolese R, Poisson R, Pilch Y, Redmond C, Fisher E, Wolmark N, Deutsch M, Montague E, et al. Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med. 1985;312:665–673. - PubMed
    1. Kurtz JM, Miralbell R. Radiation therapy and breast conservation: cosmetic results and complications. Semin Radiat Oncol. 1992;2:125–131. doi: 10.1016/1053-4296(92)90016-E. - DOI - PubMed
    1. Whelan TJ, Levine M, Julian J, Kirkbride P, Skingley P, for the Ontario Clinical Oncology Group The effects of radiation therapy on quality of life of women with breast carcinoma: Results of a Randomized Trial. Cancer. 2000;88:2260–2266. doi: 10.1002/(SICI)1097-0142(20000515)88:10<2260::AID-CNCR9>3.0.CO;2-M. - DOI - PubMed
    1. Turesson I, Nyman J, Holmberg E, Oden A. Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys. 1996;36:1065–1075. doi: 10.1016/S0360-3016(96)00426-9. - DOI - PubMed
    1. Fernando IN, Ford HT, Powles TJ, Ashley S, Glees JP, Torr M, Grafton D, Harmer CL. Factors affecting acute skin toxicity in patients having breast irradiation after conservative surgery: a prospective study of treatment practice at the Royal Marsden Hospital. Clin Oncol (R Coll Radiol) 1996;8:226–233. doi: 10.1016/S0936-6555(05)80657-0. - DOI - PubMed

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