雌激素受体α基因单核苷酸多态性与中国陕西地区汉族人群子宫内膜癌的相关性研究

Association between single nucleotide polymorphisms in the estrogen receptor α gene and endometrial cancer in Han population of Shaanxi province,China

目的:探讨雌激素受体α(estrogen receptorα,ERα)基因exon 4的A908G、C926T、G933A、C975G 4个单核苷酸多态性(single nucleotide polymorphisms,SNPs)与子宫内膜癌易感性的相关性。方法:基于人群的病例-对照研究,通过PCR产物直接测序法鉴定中国陕西地区汉族89例子宫内膜癌与115例良性病变组织的这4个SNPs的基因型,采用Logistic回归模型分析两组基因型与等位基因频率的分布,确定SNP位点基因型与子宫内膜癌临床病理特征的相关性。结果:所有组织的ERα基因3个位点SNPs均呈A908A、C926C、G933G野生型;而exon 4 C975G位点SNP呈三种基因型形式,其频率分布在两组均达到Hardy-Weinberg遗传平衡(P>0.05),说明具有群体代表性。两组975 G等位基因的发生频率分别为48.9%和51.7%,均>1%,说明均存在exon 4位点C975G SNP。两组间基因型与等位基因频率均无显著性差异(P>0.05),说明位点C975G SNP与子宫内膜癌的危险性无关。ERα基因C975G SNP基因型与临床病理特征无相关性(P>0.05)。结论:首先在中国人子宫内膜癌和对照组中发现ERα基因exon 4突变975 G等位基因,发生频率分别为48.9%和51.7%,均>1%,但C975G SNP与子宫内膜癌的危险性无关;且提示ERα基因的多态性可能具有肿瘤类型和种族的特异性。首先在中国人子宫内膜癌和对照组中未发现ERα基因exon 4位点A908G、C926T、G933A 3个SNPs,表明这些位点多态性在子宫内膜癌病人中并不常见。

Objective:To explore the association between four single nucleotide polymorphisms(SNPs)in the ERαand endometrial cancer by analyzing those SNPs in cancerous and control endometrial tissues.Methods:We evaluated the association between four SNPs in the ERαand endometrial cancer risk among 89 cases and 115 controls in a population-based,case-ontrol study conducted in Shaanxi,China.The expected DNA fragments of four SNPs(A908G,C926T,G933A,C975G),in exon 4 of the ERαgene were amplified by polymerase chain reaction(PCR)methods,and followed by sequencing and genotyping.Subsequently,the distribution of genotyping and frequency of allele between endometrial cancer cases and controls were analyzed.The associations between SNPs and clinical pathologic characteristics were further analyzed using Logistic regression model.Results:Three SNPs indicated wild genotypes as A908A,C926C,G933G in exon 4 of the ERαgene in 89 endometrial cancer and 115 normal tissues,whereas C975G SNP demonstrated three genotypes in exon 4.The frequency of the three C975G allelic variants was in Hardy-Weinberg equilibrium(P>0.05),suggesting the representatives of whole population.The frequency of 975 G allele was 48.9%and 51.7%in endometrial cancer patients and controls,respectively,great than 1%frequency implying that C975G SNP in exon 4 was informative.There was no statistically significance for any genotypes and alleles between two groups(P>0.05),indicating that C975G SNP had no association with the development of endometrial cancer.Our analysis also suggested that C975G SNP was not associated with clinical pathologic characteristics(P>0.05).Conclusion:It is the first time that 975 G allelic variant in exon 4 of the ERαgene is reported in Chinese women with endometrial cancer and controls.The frequency of 975 G allelic variant were all>1%in two groups and may be cancer type and population specific.C975G SNP is not associated with endometrial cancer.It is also first time we report that A908G,C926T,G933A SNPs are not detected in exon 4 of the ERαgene in Chinese women,suggesting that these SNPs may not be the common SNPs and not associated with endometrial cancer in Chinese population.