FTO多态性与乳腺癌易感性的荟萃分析

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

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。

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%（2/1.035-1.488, 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 0.80%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.