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

doi:10.3877/cma.j.issn.2095-5820.2017.03.009

Abstract

Abstract:

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

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]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2017, 05(03): 165-170.

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References 18

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文献	年份	人种	SNP位点	样本量		HWE P值
文献	年份	人种	SNP位点	乳腺癌组	健康对照组	HWE P值
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
Kusinska等^[15]	2012	高加索人	rs9930506	134	367	0.50
da Cunha等^[11]	2013	多种混合	rs9939609	100	148	0.31
da Cunha等^[11]	2013	多种混合	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
Mojaver等^[16]	2015	高加索人	rs1477196	62	62	0.64
Zeng等^[17]	2015	亚洲人	rs9939609	536	537	0.70^a
			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

文献	年份	人种	SNP位点	样本量		HWE P值
文献	年份	人种	SNP位点	乳腺癌组	健康对照组	HWE P值
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
Kusinska等^[15]	2012	高加索人	rs9930506	134	367	0.50
da Cunha等^[11]	2013	多种混合	rs9939609	100	148	0.31
da Cunha等^[11]	2013	多种混合	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
Mojaver等^[16]	2015	高加索人	rs1477196	62	62	0.64
Zeng等^[17]	2015	亚洲人	rs9939609	536	537	0.70^a
			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

遗传模型		相关性检验			固定/随机效应模型	异质性检验
遗传模型		OR	95%CI	P值	固定/随机效应模型	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

遗传模型		相关性检验			固定/随机效应模型	异质性检验
遗传模型		OR	95%CI	P值	固定/随机效应模型	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

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