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Role of XRCC3, XRCC1 and XPD single-nucleotide polymorphisms in survival outcomes following adjuvant chemotherapy in early stage breast cancer patients

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Abstract

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.

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Acknowledgments

ESMO Foundation awarded Elena Castro with an IMPAKT 2010 travel grant for the presentation of this work. We are grateful to Dr. Joo Ern Ang (Sutton, UK) for the editorial assistance provided.

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Authors and Affiliations

  1. Department of Medical Oncology, Hospital Universitario de Salamanca, Paseo San Vicente, CP 37007, Salamanca, Spain

    E. Castro & J. J. Cruz

  2. Cancer Investigation Center (IBMCC), University of Salamanca-CSIC, Salamanca, Spain

    E. Castro, A. Garcia & R. González-Sarmiento

  3. Prostate Cancer and GU Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    D. Olmos

  4. Molecular Medicine Unit, Department of Medicine, University of Salamanca, Salamanca, Spain

    R. González-Sarmiento

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  1. E. Castro
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Correspondence to E. Castro.

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Castro, E., Olmos, D., Garcia, A. et al. Role of XRCC3, XRCC1 and XPD single-nucleotide polymorphisms in survival outcomes following adjuvant chemotherapy in early stage breast cancer patients. Clin Transl Oncol 16, 158–165 (2014). https://doi.org/10.1007/s12094-013-1055-8

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