Long-term biomonitoring of breast cancer patients under adjuvant chemotherapy: the comet assay as a possible predictive factor

作者: E. Uriol , M. Sierra , M. A. Comendador , J. Fra , P. Martínez-Camblor

DOI: 10.1093/MUTAGE/GES050

关键词:

摘要: Most chemotherapy treatments induce DNA damage in the exposed patients. Using comet assay and peripheral blood mononuclear cells (PBMC), we have quantified this induced studied its relationship with GSTM1 GSTT1 polymorphisms, clinical parameters. For purpose, 29 Caucasian women, breast cancer patients under CMF or CEF adjuvant were included study. The parameters considered (i) therapies side effects, like haematological biochemical toxicities, (ii) prognostic predictive factors, hormonal receptor expression, tumour differentiation degree, sickness stage, nodal status, (iii) effectiveness of measured as five years relapse probability. results also related to confounding factor age. Comet indicate that 13 characterised by absence strand breaks, 16 presented breaks along treatment. Relationships between variables parameters, found principal component analysis, correlations, one-way ANOVA multivariate logistic regression analyses revealed that: (1) baseline levels are genotype expression; (2) influences after chemotherapy, it does AST level; (3) tail moment values cycle 6.1 stage might predict at years: for Stage, OR = 13.8 (IIB versus I+IIA), 95% CI 0.80-238.97, TM, 1.3, 95%, 0.97-1.79, a potential model (10* Stage (I-IIA 0, IIB 1) + cycle), has good capacity, an area ROC curve 0.872 (CI 0.62-1.00). To our knowledge, is first time such value assay. Nevertheless, before could be used tool oncologists, should confirmed more patients, problems standardisation data interpretation solved.

参考文章(82)
S. Colleu-Durel, N. Guitton, K. Nourgalieva, F. Legue, J. Lévêque, B. Danic, C. Chenal, Alkaline single-cell gel electrophoresis (comet assay): a simple technique to show genomic instability in sporadic breast cancer European Journal of Cancer. ,vol. 40, pp. 445- 451 ,(2004) , 10.1016/J.EJCA.2003.09.033
Ji???? Grim, Jaroslav Chl??dek, Ji??ina Mart??nkov??, Pharmacokinetics and pharmacodynamics of methotrexate in non-neoplastic diseases. Clinical Pharmacokinectics. ,vol. 42, pp. 139- 151 ,(2003) , 10.2165/00003088-200342020-00003
Fred F. Kadlubar, Soheila Korourian, Patricia A. Thompson, Angie Stone, Brian F. Coles, Carol Sweeney, Gail Y. McClure, Manal Y. Fares, Christine B. Ambrosone, Laura F. Hutchins, Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer. Cancer Research. ,vol. 61, pp. 7130- 7135 ,(2001)
S Pemble, K R Schroeder, S R Spencer, D J Meyer, E Hallier, H M Bolt, B Ketterer, J B Taylor, Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochemical Journal. ,vol. 300, pp. 271- 276 ,(1994) , 10.1042/BJ3000271
Petra Schütz, Walther Vogel, Günter Speit, Elke Eberhardt, Rolf Kreienberg, Sylvia Bochum, Andreas Rothfuss, Tanja Volm, Induced Micronucleus Frequencies in Peripheral Lymphocytes as a Screening Test for Carriers of a BRCA1 Mutation in Breast Cancer Families Cancer Research. ,vol. 60, pp. 390- 394 ,(2000)
Ricarda Thier, Thomas Brüning, Peter H. Roos, Hans-Peter Rihs, Klaus Golka, Yon Ko, Hermann M. Bolt, Markers of genetic susceptibility in human environmental hygiene and toxicology: The role of selected CYP, NAT and GST genes International Journal of Hygiene and Environmental Health. ,vol. 206, pp. 149- 171 ,(2003) , 10.1078/1438-4639-00209
P Poikonen, T Saarto, J Lundin, H Joensuu, C Blomqvist, Leucocyte nadir as a marker for chemotherapy efficacy in node-positive breast cancer treated with adjuvant CMF British Journal of Cancer. ,vol. 80, pp. 1763- 1766 ,(1999) , 10.1038/SJ.BJC.6690594
Stanley Lemeshow, David W. Hosmer, Applied Logistic Regression ,(1989)
Nevenka Kopjar, Vera Garaj-Vrhovac, Ivan Milas, Assessment of chemotherapy-induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay Teratogenesis Carcinogenesis and Mutagenesis. ,vol. 22, pp. 13- 30 ,(2002) , 10.1002/TCM.1035