MDM2 基因启动子区 rs2279744 位点单核苷酸多态性 与乳腺癌发病关系的 Meta 分析
| 作者: |
1武亚运,
1董晓强,
1王勇攀,
1王进,
1张志,
1毛德利,
1何宋兵
1 浙江省嘉善县第一人民医院 普通外科，浙江 嘉善 314100;2. 苏州大学附属第一医院 普通外科，江苏 苏州 215006 |
| 通讯: |
武亚运
Email: wuyayun@pwtt.com |
| DOI: | 10.3978/.10.3978/j.issn.1005-6947.2017.11.009 |
摘要
目的: 探讨鼠双微体基因(MDM2)启动子区 rs2279744 位点单核苷酸多态性与乳腺癌发病风险的关系。
方法: 检索多个国内外文献数据库，收集 MDM2 启动子区 rs2279744 位点基因多态性与乳腺癌的风险关系的 病例对照研究，筛选出符合标准的文献，提取数据后行 Meta 分析，并对结果进行敏感性分析与发表偏倚评价。
结果: 共纳入 28 篇文献，共计乳腺癌病例组 11 804 例，对照组 15 209 例。Meta 分析结果显示，总人群 中突变型与野生型(TG/GG vs. TT)与等位基因(G vs. T)均有明显差异(OR=1.15，95% CI=1.06~1.24， P<0.001;OR=1.12，95%=1.05~1.18，P<0.001); 按 洲 别 分 亚 组 分 析 显 示， 两 者 仅 在 亚 洲 人 群 中 有 明 显 差 异(TG/GG vs. TT: 随 机 效 应 模 型 OR=1.34，95% CI=1.15~1.57，P<0.001， 固 定 效 应 模 型 OR=1.34，95% CI=1.20~1.50，P<0.001;G vs. T: 随 机 效 应 模 型 OR=1.21，95% CI=1.09~1.35， P=0.001)。敏感性分析与 Egger 检验显示结论可靠，无明显偏倚。
结论: 亚洲人群 MDM-2 基因 rs2279744 位点的突变纯合子 / 杂合子(GG/TG)型相对于野生型(TT)
的个体乳腺癌发病风险增加，MDM-2 基因 rs2279744 位点的突变与亚洲人群乳腺癌密切相关。
关键词：
乳腺肿瘤
原癌基因蛋白质 c-mdm2
多态性，单核苷酸
Meta 分析
方法: 检索多个国内外文献数据库，收集 MDM2 启动子区 rs2279744 位点基因多态性与乳腺癌的风险关系的 病例对照研究，筛选出符合标准的文献，提取数据后行 Meta 分析，并对结果进行敏感性分析与发表偏倚评价。
结果: 共纳入 28 篇文献，共计乳腺癌病例组 11 804 例，对照组 15 209 例。Meta 分析结果显示，总人群 中突变型与野生型(TG/GG vs. TT)与等位基因(G vs. T)均有明显差异(OR=1.15，95% CI=1.06~1.24， P<0.001;OR=1.12，95%=1.05~1.18，P<0.001); 按 洲 别 分 亚 组 分 析 显 示， 两 者 仅 在 亚 洲 人 群 中 有 明 显 差 异(TG/GG vs. TT: 随 机 效 应 模 型 OR=1.34，95% CI=1.15~1.57，P<0.001， 固 定 效 应 模 型 OR=1.34，95% CI=1.20~1.50，P<0.001;G vs. T: 随 机 效 应 模 型 OR=1.21，95% CI=1.09~1.35， P=0.001)。敏感性分析与 Egger 检验显示结论可靠，无明显偏倚。
结论: 亚洲人群 MDM-2 基因 rs2279744 位点的突变纯合子 / 杂合子(GG/TG)型相对于野生型(TT)
的个体乳腺癌发病风险增加，MDM-2 基因 rs2279744 位点的突变与亚洲人群乳腺癌密切相关。
Association between single nucleotide polymorphisms of rs2279744 locus in MDM2 promoter region and risk of breast cancer: a Meta-analysis
CorrespondingAuthor:Wu Yayun Email: wuyayun@pwtt.com
Abstract
Objective: To investigate the association between the single nucleotide polymorphisms (SNPs) of rs2279744 locus in the promoter region of mouse double minute 2 homolog (MDM2) gene and risk of breast cancer.
Methods: Case-control studies regarding the association between the SNPs of MDM2 rs2279744 locus and risk of breast cancer were collected by searching several national and international databases. e eligible studies were screened out according to the criteria. Meta-analysis was performed following data extraction, and the sensitivity and publication bias were also analyzed.
Results: Twenty-eight case-control studies were included, with 11 804 breast cancer patients in case group and 152 09 subjects in control group. e results of Meta-analysis showed that there were signi cant di erences in mutant genotype and wild genotype (TG/GG vs. TT) as well as in alleles (G vs. T) in the overall population (OR=1.15, 95% CI=1.06–1.24, P<0.001; OR=1.12, 95% CI=1.05–1.18, P<0.001); subgroup analysis divided by di erent continents reveal that those di erences only found in Asia’s population (TG/GG vs. : OR=1.34, 95% CI=1.15–1.57, P<0.001 by random effects model, OR=1.34, 95% CI=1.20–1.50, P<0.001 by fixed effect model; G vs. T: OR=1.21, 95% CI=1.09–1.35, P=0.001 by random e ects model). e sensitivity analyses and Egger’s tests veri ed the reliable conclusions and no obvious publication biases.
Conclusion: Asian individuals with mutant genotype homozygote (GG) and heterozygous (TG) in MDM2 rs2279744 locus have a higher risk of breast cancer than those with wild genotype ( ). Mutations in MDM2 rs2279744 locus are closely associated with the risk of breast cancer in Asians.
Keywords：
Breast Neoplasms
Proto-Oncogene Proteins c-mdm2
Polymorphism
Single Nucleotide
Meta-Analysis
Methods: Case-control studies regarding the association between the SNPs of MDM2 rs2279744 locus and risk of breast cancer were collected by searching several national and international databases. e eligible studies were screened out according to the criteria. Meta-analysis was performed following data extraction, and the sensitivity and publication bias were also analyzed.
Results: Twenty-eight case-control studies were included, with 11 804 breast cancer patients in case group and 152 09 subjects in control group. e results of Meta-analysis showed that there were signi cant di erences in mutant genotype and wild genotype (TG/GG vs. TT) as well as in alleles (G vs. T) in the overall population (OR=1.15, 95% CI=1.06–1.24, P<0.001; OR=1.12, 95% CI=1.05–1.18, P<0.001); subgroup analysis divided by di erent continents reveal that those di erences only found in Asia’s population (TG/GG vs. : OR=1.34, 95% CI=1.15–1.57, P<0.001 by random effects model, OR=1.34, 95% CI=1.20–1.50, P<0.001 by fixed effect model; G vs. T: OR=1.21, 95% CI=1.09–1.35, P=0.001 by random e ects model). e sensitivity analyses and Egger’s tests veri ed the reliable conclusions and no obvious publication biases.
Conclusion: Asian individuals with mutant genotype homozygote (GG) and heterozygous (TG) in MDM2 rs2279744 locus have a higher risk of breast cancer than those with wild genotype ( ). Mutations in MDM2 rs2279744 locus are closely associated with the risk of breast cancer in Asians.