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Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy

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Tumor Biology

Abstract

This study investigated the associations between genetic polymorphisms of six genes involved in DNA repair, detoxification pathways, and fluoropyrimidine metabolism and clinical outcomes in MGC patients receiving EOF treatment. This retrospective study included 108 Chinese MGC patients receiving EOF as first-line chemotherapy. Nine single nucleotide polymorphisms (SNPs) of six genes (ERCC1 rs2298881, ERCC2 rs13181 and rs1799793, XRCC1 rs25487 and rs25489, GSTP1 rs1695, GSTT1 rs2266637, and MTHFR rs1801133 and rs1801131) were genotyped, and the associations between each SNP and clinical outcome were analyzed. XRCC1 rs25487 A allele was significantly associated with progression disease (PD) to EOF (p = 0.002), and patients with AA genotype had significantly poorer progression-free survival (PFS) (p = 0.001) and overall survival (OS) (p = 0.041) compared with patients with the G allele (GG + GA). ERCC2 rs13181 G allele was significantly associated with PD (p = 0.026), and G carriers (GG + GT) tended to have poorer PFS (p = 0.092) than TT homozygotes. ERCC2 rs1799793 GA genotype was associated with unfavorable PFS (p = 0.034) and a tendency toward poorer OS (p = 0.090) compared with GG homozygotes. Patients were categorized as either good (0 risk factors) or poor risk (≥1 unfavorable SNPs) using a prognostic index based on XRCC1 rs25487 AA, ERCC2 rs13181 (GG + GT), and ERCC2 rs1799793 GA genotypes, with median OS and PFS of 534 days, 281 days (p = 0.009) and 206 days, and 123 days (p < 0.001), respectively. These results suggest that the prognostic index comprising XRCC1 rs25487, ERCC2 rs13181, and rs1799793 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with EOF.

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Acknowledgments

The authors thank Wenyuan Zhu and Yan Yan for their help in data selection. This work supported by the Natural Science Foundation of Shanghai (Grant No. 13ZR1408200) and Foundation of the Shanghai Municipal Science and Technology Commission (Grant No. 134119a8600).

Compliance with ethical standards

The study was conducted complying with the principles of the Helsinki Accord, and informed consent was obtained from each patient.

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None

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    Authors and Affiliations

    1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

      Rujiao Liu, Xiaoying Zhao, Xin Liu, Zhiyu Chen, Lixin Qiu, Ruixuan Geng, Weijian Guo, Jiliang Yin, Jin Li & Xiaodong Zhu

    2. Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong’An Road, Shanghai, 200032, People’s Republic of China

      Rujiao Liu, Xiaoying Zhao, Xin Liu, Zhiyu Chen, Lixin Qiu, Ruixuan Geng, Weijian Guo, Jiliang Yin, Jin Li & Xiaodong Zhu

    3. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, China

      Guang He

    4. Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China

      Guang He

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    1. Rujiao Liu
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    Correspondence to Xiaodong Zhu.

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    Rujiao Liu and Xiaoying Zhao contributed equally to this work.

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    Liu, R., Zhao, X., Liu, X. et al. Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy. Tumor Biol. 37, 1753–1762 (2016). https://doi.org/10.1007/s13277-015-3935-8

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