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Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma

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Tumor Biology

Abstract

A possible association between multiple drug resistance 1 gene (MDR1) polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is currently under debate, and evidence from various epidemiological studies has yielded controversial results. To derive a more precise estimation of the association between MDR1 polymorphisms and HCC risk, the present meta-analysis was performed. A total of 8 studies containing 11 cohorts with 4407 cases and 4436 controls were included by systematic literature search of EMBASE, PubMed, Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type alleles. In particular, the variation type, functional impact, and protein domain location of the polymorphisms were assessed and used as stratified indicators. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the association. Overall, our results suggested that the mutant alleles of the MDR1 gene were associated with a significantly increased risk for HCC under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20–1.36, P < 0.001; dominant model: OR = 1.27, 95 % CI = 1.16–1.38, P < 0.001; recessive model: OR = 1.59, 95 % CI = 1.36–1.85, P < 0.001). Furthermore, increased risks for HCC were also revealed in stratified analyses by ethnicity, sample size, and quality scores of cohorts as well as variation type, functional impact, and protein domain location of polymorphisms. In conclusion, the present meta-analysis suggested that the presence of MDR1 mutant alleles might be a risk factor for HCC.

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Conflicts of interest

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Financial support

This work was supported by the Major Program of NSFC (No. 81030038), National Key Sci-Tech Project (2012ZX10002011-002), National Natural Science Foundation of China (Nos. 81372648, 81272730, 81272725), FANEDD (No. 201183), and Shanghai “Promising Youth Medical Worker” Project (No. 13Y055).

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    Authors and Affiliations

    1. Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical College, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China

      Zhi-Chao Wang, Long-Zi Liu, Jie-Yi Shi, Liu-Xiao Yang, Meng Duan, Xiao-Ying Wang, Jian Zhou, Jia Fan & Qiang Gao

    2. Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China

      Zhi-Chao Wang, Long-Zi Liu, Jie-Yi Shi, Liu-Xiao Yang, Meng Duan, Xiao-Ying Wang, Jian Zhou, Jia Fan & Qiang Gao

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

      Xin-Yang Liu

    4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

      Xin-Yang Liu

    5. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China

      Jin-Jing Hu & Yong-Na Wu

    6. Institute of Biomedical Sciences, Fudan University, Shanghai, China

      Jian Zhou & Jia Fan

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    1. Zhi-Chao Wang
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    Correspondence to Qiang Gao.

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    Zhi-Chao Wang, Long-Zi Liu and Xin-Yang Liu contributed equally to this work.

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    Additional file 1

    PRISMA 2009 checklist of this systematic review and meta-analysis. (DOCX 32 kb)

    Additional file 2

    MDR1 protein sequence annotation from Uniprot website. (DOCX 108 kb)

    Additional file 3

    Selection of the related studies. (GIF 46 kb)

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    Additional file 4

    List of included studies. (DOCX 106 kb)

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    Wang, ZC., Liu, LZ., Liu, XY. et al. Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma. Tumor Biol. 36, 7007–7015 (2015). https://doi.org/10.1007/s13277-015-3407-1

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