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Tumor Biology

, Volume 36, Issue 9, pp 7007–7015 | Cite as

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

  • Zhi-Chao Wang
  • Long-Zi Liu
  • Xin-Yang Liu
  • Jin-Jing Hu
  • Yong-Na Wu
  • Jie-Yi Shi
  • Liu-Xiao Yang
  • Meng Duan
  • Xiao-Ying Wang
  • Jian Zhou
  • Jia Fan
  • Qiang Gao
Research Article

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.

Keywords

Gene polymorphism Hepatocellular carcinoma Meta-analysis Multiple drug resistance 1 gene 

Notes

Conflicts of interest

None

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).

Supplementary material

13277_2015_3407_MOESM1_ESM.docx (32 kb)
Additional file 1 PRISMA 2009 checklist of this systematic review and meta-analysis. (DOCX 32 kb)
13277_2015_3407_MOESM2_ESM.docx (108 kb)
Additional file 2 MDR1 protein sequence annotation from Uniprot website. (DOCX 108 kb)
13277_2015_3407_Fig3_ESM.gif (47 kb)
Additional file 3

Selection of the related studies. (GIF 46 kb)

13277_2015_3407_MOESM3_ESM.tif (791 kb)
High Resolution Image (TIFF 791 kb)
13277_2015_3407_MOESM4_ESM.docx (107 kb)
Additional file 4 List of included studies. (DOCX 106 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zhi-Chao Wang
    • 1
    • 2
  • Long-Zi Liu
    • 1
    • 2
  • Xin-Yang Liu
    • 3
    • 4
  • Jin-Jing Hu
    • 5
  • Yong-Na Wu
    • 5
  • Jie-Yi Shi
    • 1
    • 2
  • Liu-Xiao Yang
    • 1
    • 2
  • Meng Duan
    • 1
    • 2
  • Xiao-Ying Wang
    • 1
    • 2
  • Jian Zhou
    • 1
    • 2
    • 6
  • Jia Fan
    • 1
    • 2
    • 6
  • Qiang Gao
    • 1
    • 2
  1. 1.Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education)Fudan UniversityShanghaiChina
  3. 3.Department of Medical OncologyFudan University Shanghai Cancer CenterShanghaiChina
  4. 4.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  5. 5.Department of General SurgeryThe First Hospital of Lanzhou UniversityLanzhouChina
  6. 6.Institute of Biomedical SciencesFudan UniversityShanghaiChina

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