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Polymorphisms in IGF2/H19 gene locus are associated with platinum-based chemotherapeutic response in Chinese patients with epithelial ovarian cancer

    Ying Zeng

    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China

    Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China

    ,
    Tai-Lin Li

    Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510289, PR China

    ,
    Hai-Bo Zhang

    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China

    Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China

    ,
    Jun-Li Deng

    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China

    Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China

    ,
    Rui Zhang

    Department of Pharmacy, the Second People's Hospital of Anhui Province, Hefei 230041, PR China

    ,
    Hong Sun

    Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, PR China

    ,
    Zi-Rui Wan

    Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, PR China

    ,
    Ying-Zi Liu

    ***Author for correspondence:

    E-mail Address: yzliu2005@sina.com

    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China

    Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China

    ,
    Yuan-Shan Zhu

    **Author for correspondnece:

    E-mail Address: yuz2002@med.cornell.edu

    Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA

    &
    Guo Wang

    *Author for correspondence: Tel.: +86 731 84805380; Fax: +86 731 82354476;

    E-mail Address: 207082@csu.edu.cn

     

    Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, PR China

    Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China

    Published Online:https://doi.org/10.2217/pgs-2018-0153

    Aim: The present study aimed to assess the association between IGF2/H19 genetic variants and susceptibility to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Methods: A total of 43 platinum-resistant (PR) and 138 platinum-sensitive (PS) EOC patients were recruited in our study. 21 polymorphisms in IGF2/H19 locus were genotyped by Sequenom MassARRAY assay. Results: The frequencies of GG genotype in both rs3842761(C/G) and rs4244809(A/G) were significantly lower in PR group compared with those in PS group (9.76 vs 23.36%, p = 0.049; 9.76 vs 26.09%, p = 0.045; respectively). Compared with the AA genotype, rs4244809 GG genotype was associated with significantly reduced risk of platinum resistance (adjusted OR: 0.30; 95% CI: 0.10–0.91; p = 0.033). Further stratified analyses revealed that the SNPs of rs3842761 and rs4244809 were greatly related to PR risk in FIGO stage III–IV (rs3842761GG/CC+CG: adjusted OR: 0.15; 95% CI: 0.02–1.21; rs4244809 GG/AA+AG: adjusted OR: 0.24; 95% CI: 0.07–0.84; respectively) and serous adenocarcinoma subgroups (rs3842761 GG/CC+CG: adjusted OR: 0.21; 95% CI: 0.05–0.94; rs4244809 GG/AA+AG: adjusted OR: 0.19; 95% CI: 0.04–0.5; respectively), while rs7924316 polymorphism was associated with reduced risk of PR in serous adenocarcinoma subgroup as analyzed by a recessive model (rs7924316 GG/TT+TG: adjusted OR: 0.22; 95% CI: 0.05–0.98). In addition, both TCT haplotypes of rs3741206/rs3842761/rs7924316 and TC haplotype of rs3741206/rs3842761 were associated with elevated risk of PR (for the TCT haplotype of rs3741206/rs3842761/rs7924316: p = 0.049; OR: 1.69; 95% CI: 1.00–2.87; for the TC haplotype of rs3741206/rs3842761: p = 0.044; OR: 1.71; 95% CI: 1.01–2.88). Conclusion: These results suggest that polymorphisms in IGF2/H19 gene locus are associated with PR risk in EOC.

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