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Polymorphisms in the base excision repair pathway modulate prognosis of platinum-based chemotherapy in advanced non-small cell lung cancer

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Abstract

Purpose

Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy.

Methods

We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy.

Results

Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11–5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02–3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12–0.92).

Conclusions

We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.

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Acknowledgments

This work was supported in part by grants from the Education Department of Jiangsu Province Green Blue Project (2010), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry 2009 (IA09), the National Natural Science Foundation of China (81071643), the National Natural Science Foundation of China (30772549), the Surface Project of the Health Department of Jiangsu Province (H201001) and the Innovation Project of Jiangsu Province.

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Authors and Affiliations

  1. Department of Oncology, BenQ Medical Center, Nanjing Medical University, Suzhou, 215000, China

    Wan Zhao

  2. Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 210029, China

    Lingmin Hu, Hongbing Shen, Zhibin Hu & Hongxia Ma

  3. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Jiali Xu, Yongqian Shu & Yongmei Yin

  4. Department of Thoracic and Cardiac Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Yongfeng Shao

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  1. Wan Zhao
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Correspondence to Yongfeng Shao or Yongmei Yin.

Additional information

Wan Zhao, Lingmin Hu and Jiali Xu contributed equally to this work.

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Zhao, W., Hu, L., Xu, J. et al. Polymorphisms in the base excision repair pathway modulate prognosis of platinum-based chemotherapy in advanced non-small cell lung cancer. Cancer Chemother Pharmacol 71, 1287–1295 (2013). https://doi.org/10.1007/s00280-013-2127-8

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  • DOI: https://doi.org/10.1007/s00280-013-2127-8

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