Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma
Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma
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多重耐药1基因MDR1基因多态性与肝癌风险
DOI：
10.1007/s13277-015-3407-1
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Gao Qiang
中科院分区：
文献类型：
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作者：
Wang Zhi-Chao;Liu Long-Zi;Liu Xin-Yang;Hu Jin-Jing;Wu Yong-Na;Shi Jie-Yi;Yang Liu-Xiao;Duan Meng;Wang Xiao-Ying;Zhou Jian;Fan Jia;Gao Qiang
多药耐药1基因（MDR1）多态性与发生肝细胞癌（HCC）风险之间的可能关联目前尚存在争议，各种流行病学研究的证据产生了有争议的结果。为了更精确地估计MDR1多态性与HCC风险之间的关系，本研究进行了荟萃分析。通过EMBASE、PubMed、Web of Science和中国知网的系统文献检索，共纳入8篇研究，共11个队列，4407例，对照4436例。所有多态性均被归类为突变型/野生型等位基因。特别是，对多态性的变异类型、功能影响和蛋白质结构域位置进行了评估，并将其作为分层指标。计算95%置信区间（CI）的合并优势比（OR）来评估相关性。总体而言，我们的结果表明，在所有遗传模型下，MDR1基因突变等位基因与HCC风险显著增加相关（等位基因模型：OR = 1.28, 95% CI = 1.20-1.36，P< 0.001；显性模型：OR = 1.27, 95% CI = 1.16-1.38，P< 0.001；隐性模型：OR = 1.59, 95% CI = 1.36-1.85，P< 0.001）。此外，根据种族、样本量、队列质量评分、变异类型、功能影响和多态性的蛋白质结构域位置进行分层分析，也揭示了HCC风险的增加。总之，目前的荟萃分析表明，MDR1突变等位基因的存在可能是HCC的危险因素。
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.