2024-03-28T18:58:56Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1345792018-09-05T08:56:29Zcom_10261_112com_10261_1col_10261_365
DIGITAL.CSIC
author
Castro, Elena
author
Cruz, Juan Jesús
author
González-Sarmiento, Rogelio
funder
European Society for Medical Oncology
2016-07-07T11:30:00Z
2016-07-07T11:30:00Z
2014
Clinical and Translational Oncology 16(2): 158-165 (2014)
http://hdl.handle.net/10261/134579
10.1007/s12094-013-1055-8
http://dx.doi.org/10.13039/501100007075
[Introduction]: Anthracyclines have various mechanisms of action that in the end lead to DNA double-strand breaks. Single-nucleotide polymorphisms (SNPs) in DNA repair genes may alter the protein function, affecting DNA repair proficiency and, therefore, the efficiency of DNA damaging chemotherapy. We have analysed whether SNPs in DNA repair genes (XRCC1, XRCC3 and XPD) could be useful to predict the response to anthracyclines in patients with early-stage breast cancer (EBC). Methods: Peripheral blood samples from 150 patients with EBC were used for genotyping XRCC3Thr241Met, XRCC1Arg399Gln and XPDLys751Gln. Genotypes were correlated with survival outcomes. [Results]: Eighty-four patients received treatment with chemotherapy regimens containing anthracyclines. In this group, patients with XRCC1Arg399Arg had a significant improvement in 5-year Disease Free Survival (DFS) compared with those with the Arg/Gln and Gln/Gln variants (84 vs 46 %, p = 0.026). In the multivariate analysis, XRCC1Arg399Arg was reported as an independent prognostic factor for DFS (HR 0.4, CI-95 % 0.2-0.9, p = 0.035). Patients with the XRCC3 Met241Met genotype presented better 5-year OS than those carrying the Thr/Thr and Met/Thr variants (100 vs 70 %, p = 0.030). A multivariate analysis for OS confirmed the independent prognostic value of XRCC3 Met241Met (HR 0.15, CI-95 % 0.02-0.90, p = 0.048). These differences were not significant when patients receiving other chemotherapy treatments, different from anthracyclines, were also considered (n = 150). XPDLys751Lys was associated with older age at diagnosis than the Lys/Gln and Gln/Gln genotypes (65 vs 58 years, p < 0.0001). [Conclusions]: XRCC3Thr241Met and XRCC1Arg399Gln may be predictive of survival outcome in EBC patients treated with anthracycline-based chemotherapy regimens.
eng
closedAccess
XRCC1
Breast cancer
Adjuvant chemotherapy
XPD
XRCC3
Role of XRCC3, XRCC1 and XPD single-nucleotide polymorphisms in survival outcomes following adjuvant chemotherapy in early stage breast cancer patients
artículo
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https://digital.csic.es/bitstream/10261/134579/1/accesoRestringido.pdf
File
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42637ae8545636bc41605c1740a9a84e
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accesoRestringido.pdf