IL—1基因簇与Luminal型乳腺癌相关性研究(1)
【摘 要】目的：研究IL-1基因簇中IL-1B基因启动子区+3954位点单核营酸多态( SNP)和IL-1RN基因可变数目串联重复多态性(VNTR)与乳腺癌易感性的关系及其基因频率与乳腺癌分子分型之间的关系，方法：采用聚合酶链反应(PCR)和限制性片段长度多态性分析(RFLP)的方法，分析223名乳腺癌病人及284例当地健康对照者的IL-1B+3954基因位点和IL-1RN基因多态性，计算基因型频率(genotype frequencies)和等位基因频率(allele-frequencies)。各基因多态性位点的等位基因频率用经过x2检验确定的Hardy-Weinberg平衡检验。各等位基因的频率以及基因型的分布频率用优势比(OR)及其95%可信区间(95% CI)表示的相对风险度分析。结果：IL-IB+3954和IL-1 RN的基因型频率和等位基因频率在乳腺癌患者组和对照组之间无显著性差异((P>0.05)。各单倍型在乳腺癌患者组和对照组之间也无显著性差异((P>0.05)。在不同肿瘤增值指数组，IL-1B+3954 位点SNP基因和等位基因在不同增值指数患者中的频率分布有显著性差异((P<0.05)。结论：IL -1B+3954和IL-1RN基因多态性与乳腺癌的发病率无相关性，但可能与乳腺癌细胞的增殖指数相关。
【关键词】乳腺癌； IL-1B；IL-1RN；单核苷酸多态性
【文章编号】1004-7484(2014)07-4133-02
【Abstract】Objective： To investigate the relationship between the geneticgene singlenucleotide polymorphisms(SNPs) at positions+3954， variable number tandem repeat (VNTR) polymorphism in IL-LB gene intron 2 and risk of breastcancer，and find the association between the factor and the subtype of breastcancer.Methods： Techniques of polymerase chain reaction(PCR) and restrictionfragment length polymorphism(RFLP) ，were used to analyze the polymorphisms of IL-1B+3954 and IL-1RN in 223 cases of CP patients and 284 periodontallyhealthy controls ，and calculate their genotype frequencies and allele frequencies. Genotypes distributions were examined for significant departure from the Hardy--Weinberg equilibrium by a goodness of fit x2test.Odds ratioat 95% confidence interval (CI) were calculated to compare risk of the breast cancer between the examined genotypes.Chi squared analysis was used to examine differences in the proportion of the examined genotypes between different subgroups.Results： The genotype and allele distributions of IL-1B+3954 andIL-1RN showed the differences were not significant (P>0.05). There were also nosignificant differences between the breastcancer and control groups for the haplotypes (P>0.05). There were significant differences between the high value-added index and low value-add index for IL-1B+3954 (P<0.05). Conclusion： IL-1B+3954 andIL-1RN genotype weren’t related to patients with breast cancer； IL-1B+3954 were signif icantly relat ed to patient s with breast cancer with KI-67>14%.
【Keywords】breast cancer； interleuk in-1B； IL-l receptor antagonist ；geneticgene singlenucleotide polymorphisms
乳腺癌是一种高度异质性肿瘤。ER、PR、HER-2、KI-67 是影响乳腺癌预后及治疗的最重要分子标志物。Perou 等[1]根据不同的基因表型(ER、PR、HER-2 、KI-67状态) 将乳腺癌分成不同的分子分型。国内外研究表明[2-3]，不同分子分型的乳腺癌生物学行为不尽相同，白细胞介素- 1(IL -1B)，参与了机体炎症和免疫反应过程。IL -1B可以结合雌激素受体(ER)，导致乳腺癌细胞的转录激活，因此其在乳腺癌的发生和发展过程中起着非常重要的作用[5]。已有相关报道证明IL -1B基因上有三种单核苷酸多态性增加了乳腺癌的风险性。[6，7]IL-1B + 3954( rs1143634)即是其中之一。目前，该位点多态性与肿瘤的相关性国外已见报道[8，9]， 但其与乳腺癌的发生是否相关国内尚未报道。我们应用聚合酶链反应- 限制性片段长度多态性( polymerase chain react ion-restrict ion f ragmentlength polymorphism， PCR-RFLP) 技术和DNA 序列分析法， 对IL-1B 基因+3954T/ C 多态性进行研究， 探讨IL-1B 基因与乳腺癌易患性之间的关系。为认识乳腺癌的发病机制提供一定的实验依据，用于乳腺癌癌易感个体的预警和乳腺癌癌防。, 百拇医药(郝杰 王彦伟)
【关键词】乳腺癌； IL-1B；IL-1RN；单核苷酸多态性
【文章编号】1004-7484(2014)07-4133-02
【Abstract】Objective： To investigate the relationship between the geneticgene singlenucleotide polymorphisms(SNPs) at positions+3954， variable number tandem repeat (VNTR) polymorphism in IL-LB gene intron 2 and risk of breastcancer，and find the association between the factor and the subtype of breastcancer.Methods： Techniques of polymerase chain reaction(PCR) and restrictionfragment length polymorphism(RFLP) ，were used to analyze the polymorphisms of IL-1B+3954 and IL-1RN in 223 cases of CP patients and 284 periodontallyhealthy controls ，and calculate their genotype frequencies and allele frequencies. Genotypes distributions were examined for significant departure from the Hardy--Weinberg equilibrium by a goodness of fit x2test.Odds ratioat 95% confidence interval (CI) were calculated to compare risk of the breast cancer between the examined genotypes.Chi squared analysis was used to examine differences in the proportion of the examined genotypes between different subgroups.Results： The genotype and allele distributions of IL-1B+3954 andIL-1RN showed the differences were not significant (P>0.05). There were also nosignificant differences between the breastcancer and control groups for the haplotypes (P>0.05). There were significant differences between the high value-added index and low value-add index for IL-1B+3954 (P<0.05). Conclusion： IL-1B+3954 andIL-1RN genotype weren’t related to patients with breast cancer； IL-1B+3954 were signif icantly relat ed to patient s with breast cancer with KI-67>14%.
【Keywords】breast cancer； interleuk in-1B； IL-l receptor antagonist ；geneticgene singlenucleotide polymorphisms
乳腺癌是一种高度异质性肿瘤。ER、PR、HER-2、KI-67 是影响乳腺癌预后及治疗的最重要分子标志物。Perou 等[1]根据不同的基因表型(ER、PR、HER-2 、KI-67状态) 将乳腺癌分成不同的分子分型。国内外研究表明[2-3]，不同分子分型的乳腺癌生物学行为不尽相同，白细胞介素- 1(IL -1B)，参与了机体炎症和免疫反应过程。IL -1B可以结合雌激素受体(ER)，导致乳腺癌细胞的转录激活，因此其在乳腺癌的发生和发展过程中起着非常重要的作用[5]。已有相关报道证明IL -1B基因上有三种单核苷酸多态性增加了乳腺癌的风险性。[6，7]IL-1B + 3954( rs1143634)即是其中之一。目前，该位点多态性与肿瘤的相关性国外已见报道[8，9]， 但其与乳腺癌的发生是否相关国内尚未报道。我们应用聚合酶链反应- 限制性片段长度多态性( polymerase chain react ion-restrict ion f ragmentlength polymorphism， PCR-RFLP) 技术和DNA 序列分析法， 对IL-1B 基因+3954T/ C 多态性进行研究， 探讨IL-1B 基因与乳腺癌易患性之间的关系。为认识乳腺癌的发病机制提供一定的实验依据，用于乳腺癌癌易感个体的预警和乳腺癌癌防。, 百拇医药(郝杰 王彦伟)