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中华临床实验室管理电子杂志 ›› 2017, Vol. 05 ›› Issue (03) : 165 -170. doi: 10.3877/cma.j.issn.2095-5820.2017.03.009

所属专题： 文献；

实验研究

FTO多态性与乳腺癌易感性的荟萃分析
王亚男1, 董学君1, 徐秀平1, 屠春雨1,†()   
  1. 1. 312000　绍兴市人民医院(浙江大学绍兴医院)
  • 收稿日期:2017-05-25 出版日期:2017-08-28
  • 通信作者: 屠春雨
  • 基金资助:
    浙江省医药卫生科技计划资助项目(2015KYB407)

Association between fat mass and obesity-associated gene polymorphisms and susceptibility of breast cancer: a meta-analysis

Yanan Wang1, Xuejun Dong1, Xiuping Xu1, Chunyu Tu1,†()   

  1. 1. Shaoxing People′s Hospital (Shaoxing Hospital of Zhejiang University), Shaoxing 312000, China
  • Received:2017-05-25 Published:2017-08-28
  • Corresponding author: Chunyu Tu
  • About author:
    Corresponding author: Tu Chunyu, Email:
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引用本文：

王亚男, 董学君, 徐秀平, 屠春雨. FTO多态性与乳腺癌易感性的荟萃分析[J/OL]. 中华临床实验室管理电子杂志, 2017, 05(03): 165-170.

Yanan Wang, Xuejun Dong, Xiuping Xu, Chunyu Tu. Association between fat mass and obesity-associated gene polymorphisms and susceptibility of breast cancer: a meta-analysis[J/OL]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2017, 05(03): 165-170.

目的

评价脂肪量与肥胖相关基因(fat mass and obesity-associated gene，FTO)的多个单核苷酸多态性位点(single nucleotide polymorphisms，SNP)与乳腺癌发病的相关性。

方法

全面检索Pubmed、Embase、Web of science、中国知网(CNKI)、万方数据库及中国生物医学文献数据库(CBM)，获取11个FTO基因多态性与乳腺癌易感性的病例-对照研究，对不同SNP位点采用等位基因位点、共显性遗传模型、显性遗传模型、隐性遗传模型分别评价乳腺癌发病的相对危险度，并对异质性较大的遗传模型，进行不同人种的亚组分析。运用Meta分析方法综合评价FTO的SNP位点(rs9939609、rs1477196、rs1121980)与乳腺癌的相关性。

结果

共有6篇病例-对照研究文献被纳入，包括2994例乳腺癌患者和3699名健康对照，Meta分析结果显示：rs1477196基因多态性在显性遗传模型中与乳腺癌具有相关性(OR=1.241，95%CI为1.035~1.488，P=0.019)；rs9939609和rs1121980基因多态性与乳腺癌均无明显相关性(OR=1.062，95%CI为0.934~1.208，P=0.36)。人种亚组分析则显示rs1477196的G等位基因在亚洲人中与乳腺癌显著相关(OR=1.305，95%CI为1.085~1.569，P=0.005)，但与高加索人(OR=1.136，95%CI为0.641~2.014，P=0.662)和混合人种(OR=1.131，95%CI为0.809~1.583，P=0.472)均无相关性。

结论

FTO多态性与乳腺癌的易感性在不同遗传模型及人种中有差异。亚洲人中rs1477196的G等位基因与乳腺癌发病呈正相关。

关键词: 乳腺癌, 脂肪量与肥胖相关基因, 多态性，单核苷酸, Meta分析
Objective

To analyze the potential association between single nucleotide polymorphisms (SNP) in fat mass and obesity-associated gene (FTO) and breast cancer using meta-analysis.

Methods

Overall retrievals of PubMed, Embase, Web of Science, Wanfang, China National Knowledge and SinoMed were performed and a total of 11 case-control studies were included. The pooled odds ratios were conducted respectively for allele comparison, additive genetic model, dominant genetic model and recessive genetic model, subgroup analysis of different races was also performed. The relationship of FTO gene SNPs (rs9939609, rs1477196, rs1121980) and breast cancer was comprehensively evaluated by meta-analysis.

Results

Six case-control studies covering 2994 cases and 3699 controls were included in this meta-analysis. Pooled analysis showed that rs1477196 polymorphism in dominant genetic model increased the susceptibility of breast cancer (OR=1.241, 95%CI 1.035-1.488, P=0.019). rs9939609 and rs1121980 were not related to breast cancer (OR=1.062, 95%CI为0.934-1.208, P=0.36). Subgroup analysis of different races indicated that significant risks for rs1477196 G allele were found in the Asian population (OR=1.305, 95%CI 1.085-1.569, P=0.005), but not in the Caucasia population (OR=1.136, 95%CI 0.641-2.014, P=0.662) and mixed population (OR=1.131, 95%CI 0.809-1.583, P=0.472).

Conclusions

FTO polymorphisms may play an important role in the susceptibility of breast cancer in an ethnicity specific manner. In the Asian population, the risk of breast cancer was positively associated with the rs1477196 G allele.

Key words: Breast cancer, Fat mass and obesity-associated gene, single nucleotide polymorphism, Meta-analysis
表1 纳入文献的一般资料
文献 年份 人种 SNP位点 样本量 HWE P值
乳腺癌组 健康对照组
Kaklamani等[10] 2011 多种混合 rs9939609 302 349 0.92
rs1477196 311 358 0.91
rs7206790 315 358 0.38
rs8047395 309 355 0.86
Kusinska等[15] 2012 高加索人 rs9939609 134 357 0.66
rs9930506 134 367 0.50
da Cunha等[11] 2013 多种混合 rs9939609 100 148 0.31
rs1121980 100 148 0.62
Akilzhanova等[14] 2013 多种混合 rs1477196 315 604 0.25
Mojaver等[16] 2015 高加索人 rs9939609 62 62 0.43
rs1477196 62 62 0.64
Zeng等[17] 2015 亚洲人 rs9939609 536 537 0.70a
rs1477196 536 537 0.14 a
rs1121980 536 537 0.81 a
rs6499640 535 537 0.89 a
rs16953002 536 537 0.81 a
rs11075995 536 537 0.36 a
图1 Meta分析文献纳入流程图
表2 FTO基因在不同遗传模型下与乳腺癌易感的相关性
遗传模型 相关性检验 固定/随机效应模型 异质性检验
OR 95%CI P值 I2值(%) P值
rs9939609(T/A) ? ? ? ? ? ?
? A vs T 1.062 0.934~1.208 0.360 F 0.00 0.551
? TA vs TT 0.972 0.802~1.179 0.774 F 0.00 0.463
? AA vs TT 1.083 0.812~1.445 0.586 F 0.00 0.620
? TA/AA vs TT 1.019 0.848~1.225 0.837 F 0.00 0.458
? AA vs TA/TT 1.175 0.935~1.478 0.167 F 0.00 0.803
rs1477196(A/G) ? ? ? ? ? ?
? G vs A 1.183 0.984~1.422 0.073 R 55.10 0.083
? AG vs AA 1.210 0.999~1.466 0.051 F 0.00 0.833
? GG vs AA 1.334 0.784~2.269 0.288 R 70.80 0.016
? AG/GG vs AA 1.241 1.035~1.488 0.019 F 0.00 0.468
? GG vs AG/AA 0.882 0.377~2.066 0.773 R 92.90 <0.001
rs1121980(G/A) ? ? ? ? ? ?
? A vs G 0.985 0.676~1.436 0.939 R 68.40 0.075
? GA vs GG 1.055 0.828~1.346 0.663 F 0.00 0.372
? AA vs GG 0.991 0.408~2.403 0.984 R 68.20 0.076
? GA/AA vs GG 1.067 0.846~1.346 0.584 F 44.20 0.181
? AA vs GA/GG 1.013 0.477~2.152 0.973 R 61.00 0.109
图2 rs9939609(a)、rs1477196(b)、rs1121980(c) SNP位点与乳腺癌发病的关系
图3 rs9939609基因多态性研究漏斗图
图4 rs1477196基因多态性研究漏斗图
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