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中华乳腺病杂志(电子版) ›› 2015, Vol. 09 ›› Issue (05) : 298 -302. doi: 10.3877/cma. j. issn.1674-0807.2015.05.003

论著

细胞周期蛋白D1 G870A 基因多态性与新疆维吾尔族及汉族女性乳腺癌易感性的关系
刘炜1, 李姗1, 杨顺娥1,†()   
  1. 1.830011 乌鲁木齐,新疆医科大学附属肿瘤医院淋巴瘤与乳腺癌内科
  • 收稿日期:2015-04-16 出版日期:2015-10-01
  • 通信作者: 杨顺娥
  • 基金资助:
    国家自然科学基金资助项目(81160320)

Association between cyclin D1 G870A polymorphism and breast cancer susceptibility of Uygur and Han nationalities in Xinjiang

Wei Liu1, Shan Li1, Shun'e Yang†,1()   

  1. 1.Department of Lymphoma and Breast Cancer Internal Medicine, Tumor Hospital of Xinjiang Medical University, Urumqi 830011, China
  • Received:2015-04-16 Published:2015-10-01
  • Corresponding author: Shun'e Yang
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刘炜, 李姗, 杨顺娥. 细胞周期蛋白D1 G870A 基因多态性与新疆维吾尔族及汉族女性乳腺癌易感性的关系[J/OL]. 中华乳腺病杂志(电子版), 2015, 09(05): 298-302.

Wei Liu, Shan Li, Shun'e Yang. Association between cyclin D1 G870A polymorphism and breast cancer susceptibility of Uygur and Han nationalities in Xinjiang[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2015, 09(05): 298-302.

目的

探讨细胞周期蛋白D1(CCND1)基因第4 外显子870 位点单核苷酸多态性在维吾尔族及汉族乳腺癌患者中的分布及其与乳腺癌易感性的关系。

方法

根据纳入、排除标准,选取2012 年1 月至2014 年12 月就诊于新疆医科大学附属肿瘤医院的192 例维吾尔族女性乳腺癌患者(维吾尔族乳腺癌组)、200 例维吾尔族健康女性(维吾尔族健康对照组)、254 例汉族女性乳腺癌患者(汉族乳腺癌组)和200 例汉族健康女性(汉族健康对照组)进行前瞻性对照研究。 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测上述研究对象的CCND1 G870A 基因多态性。 CCND1 G870A 基因型分布及等位基因频率的比较采用χ2 检验,并用非条件的Logistic 回归分析该位点多态性与新疆维吾尔族、汉族乳腺癌易感性的关系。

结果

CCND1 G870A 基因GG、AG、AA 基因型及G、A 等位基因频率的分布在维吾尔族乳腺癌组与其健康对照组之间差异无统计学意义[GG、AG、AA 基因型:18.7%(36/192)比16.0%(32/200),52.1% (100/192)比49.5% (99/200),29.2% (56/192)比34.5% (69/200),χ2 =1.430,P=0.489;G、A 等位基因频率:44.8% (172/384)比40.8% (163/400),55.2% (212/384)比59.2%(237/400),χ2=1.308,P=0.253],在汉族乳腺癌组与其健康对照组之间差异也均无统计学意义[GG、AG、AA 基因型:20.1% (51/254)比16.0% (32/200)、50.0% (127/254)比56.0% (112/200)、29.9%(76/254)比28.0%(56/200),χ2 =1.925,P=0.382;G、A 等位基因频率:45.1%(229/508)比44.0%(176/400)、54.9%(279/508)比56.0%(224/400),χ2=0.105,P=0.745]。 无论是维吾尔族与汉族的乳腺癌组之间,还是维吾尔族与汉族的健康对照组之间,各基因型(χ2 =0.213,P=0.899;χ2 =0.007,P=0.932)及等位基因频率(χ2=2.153,P=0.341;χ2=0.865,P=0.352)分布的差异也均无统计学意义。 在维吾尔族和汉族人群中,携带A 等位基因者均不增加罹患乳腺癌的风险(A 等位基因比G 等位基因:OR=0.848,95% CI 0.639 ～1.125,P=0.253;OR=0.957,95% CI 0.735 ～1.246,P=0.745)。

结论

CCND1 G870A 基因多态性与新疆维吾尔族及汉族人群的乳腺癌易感性均无明显相关性。

关键词: 乳腺肿瘤, 细胞周期蛋白D1, 多态现象, 遗传, 维吾尔族

Objective

To investigate the distribution of single nucleotide polymorphism (SNP) at 870 position of exon 4 in cyclin D1 gene (CCND1)and its relationship with susceptibility to breast cancer in patients of Uygur and Han nationalities.

Methods

According to the inclusion and exclusion criteria, we enrolled 192 breast cancer patients of Uygur nationality, 200 Uygur healthy controls, 254 breast cancer patients of Han nationality and 200 Han healthy controls, who all were treated in Tumor Hospital of Xinjiang Medical University from January 2012 to December 2014, for a prospective study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the G870A polymorphism of CCND1 gene.CCND1 G870A genotype and allele frequency were compared by χ2 test. The relationship between this polymorphism and breast cancer susceptibility in Uygur or Han population in Xinjiang was analyzed using nonconditional Logistic regression.

Results

The distribution of GG, AG, AA genotypes of CCND1 gene G870A and G/A allele frequency showed no significant difference between Uygur breast cancer patients and Uygur healthy controls [GG, AG, AA genotypes: 18.7% (36/192) vs 16.0% (32/200), 52.1%(100/192) vs 49.5% (99/200), 29.2% (56/192) vs 34.5% (69/200), χ2 =1.430, P=0.489; G/A allele frequency:44.8% (172/384) vs 40.8% (163/400),55.2% (212/384) vs 59.2% (237/400), χ2=1.308, P=0.253]. The comparison between Han breast cancer patients and Han healthy controls showed the similar results [GG, AG, AA genotypes: 20.1% (51/254) vs 16.0% (32/200), 50.0% (127/254) vs 56.0% (112/200),29.9% (76/254) vs 28.0% (56/200), χ2=1.925, P=0.382; G/A allele frequency:45.1% (229/508) vs 44.0% (176/400), 54.9% (279/508) vs 56.0% (224/400), χ2 =0.105, P=0.745]. Whether Han or Uighur population, the differences in the genotype distribution (χ2 =0.213,P=0.899;χ2=0.007,P=0.932) and allele frequency (χ2=2.153,P=0.341;χ2=0.865,P=0.352) showed no significant difference between Uygur and Han breast cancer patients or between Uygur and Han healthy controls.Our finding showed no increased risk of breast cancer in the population carrying A allele in Uygur or Han population (A allele vs G allele: OR=0.848,95%CI 0.639-1.125, P=0.253; OR=0.957,95%CI 0.735-1.246, P=0.745).

Conclusion

There is no significant association between CCND1 G870A polymorphism and breast cancer susceptibility in Uygur or Han population in Xinjiang.

Key words: Breast neoplasms, Cyclin D1, Polymorphism, genetic, Uygur nationality
图1 细胞周期蛋白D1 G870A 基因扩增产物BcnI(NciI)酶切结果 注:M 为标记条带;1、2、5 条带为AG 型;3 条带为AA 型;4 条带为GG 型
图2 细胞周期蛋白D1 G870A 基因PCR 产物测序结果 注:a、b、c 图分别为GG、AG 和AA 基因型的测序结果;箭头所示等位基因突变位点
表1 维吾尔族、汉族人群细胞周期蛋白D1 G870A 基因型和等位基因频率分布
组别 例数 基因型[例(%)] 等位基因[个(频率)]
GG AG AA Ga Ab
维吾尔族
乳腺癌组 192 36(18.7) 100(52.1) 56(29.2) 172(44.8) 212(55.2)
健康对照组 200 32(16.0) 99(49.5) 69(34.5) 163(40.8) 237(59.2)
汉族
乳腺癌组 254 51(20.1) 127(50.0) 76(29.9) 229(45.1) 279(54.9)
健康对照组 200 32(16.0) 112(56.0) 56(28.0) 176(44.0) 224(56.0)
表2 细胞周期蛋白D1 G870A 基因多态性与维吾尔族人群乳腺癌危险性关系的Logistic 回归分析(n=192)
基因 回归系数 标准误 Word值 P值 OR值 95%置信区间
基因型
GG 1
AG -0.108 0.281 0.147 0.702 0.898 0.517～1.558
AA -0.327 0.302 1.167 0.280 0.721 0.399～1.305
AG+AA -0.192 0.267 0.516 0.473 0.825 0.489～1.393
等位基因
G 1
A -0.165 0.145 1.307 0.253 0.848 0.639～1.125
表3 细胞周期蛋白D1 G870A 基因多态性与汉族人群乳腺癌危险性关系的Logistic 回归分析(n=254)
基因 回归系数 标准误 Word值 P值 OR值 95%置信区间
基因型
GG 1
AG -0.340 0.260 1.713 0.191 0.711 0.427～1.185
AA -0.161 0.286 0.315 0.574 0.852 0.486～1.492
AG+AA -0.277 0.226 4.272 0.265 0.758 0.466～1.234
等位基因
G 1
A -0.044 0.135 0.105 0.745 0.957 0.735～1.246
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