文章摘要
陈霄,王金桃,白丽霞,丁玲,吴婷婷,白兰,许娟,孙雪松.宫颈癌变中叶酸缺乏与脆性组氨酸三联体基因表达异常的相互作用[J].中华流行病学杂志,2015,36(4):387-392
宫颈癌变中叶酸缺乏与脆性组氨酸三联体基因表达异常的相互作用
Interaction between folate deficiency and aberrant expression related to fragile histidine triad gene in the progression of cervical cancerization
收稿日期:2014-11-19  出版日期:2015-04-04
DOI:10.3760/cma.j.issn.0254-6450.2015.04.020
中文关键词: 宫颈肿瘤;血清叶酸;脆性组氨酸三联体基因
英文关键词: Uterine cervical neoplasms;Serum folate;Fragile histidine triad gene
基金项目:国家自然科学基金(30872166, 81273157, 81473060); 山西省自然科学基金(2008011075-1)
作者单位E-mail
陈霄 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
王金桃 030001 太原, 山西医科大学公共卫生学院流行病学教研室 wangjt59@163.com 
白丽霞 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
丁玲 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
吴婷婷 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
白兰 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
许娟 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
孙雪松 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
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中文摘要:
      目的 探讨叶酸缺乏与脆性组氨酸三联体(FHIT)基因异常表达在宫颈癌发生发展中的相互作用。方法 选取经病理学确诊的宫颈炎症(CI)患者80例、低度宫颈上皮内瘤样变(CINⅠ)患者55例、高度宫颈上皮内瘤样变(CINⅡ/Ⅲ)患者55例以及宫颈鳞状细胞癌(SCC)患者64例作为研究对象。采用微生物法测定其血清叶酸水平、甲基化特异性PCR检测FHIT基因CpG岛甲基化状况。Western blot法检测宫颈组织中FHIT蛋白的表达水平。同时采用体外细胞试验方法, 对宫颈癌细胞CaSki(HPV16阳性)进行叶酸干预, 检测不同叶酸浓度下的相关指标的变化。利用SPSS 17.0软件进行相关资料的χ2检验、Kruskal-Wallis检验、Spearman秩相关分析, 应用相加模型进行交互作用评价。结果 随着宫颈病变的加重, 血清叶酸含量逐渐降低(H=59.08, P<0.001), FHIT基因CpG岛甲基化率逐渐升高(趋势检验χ2=28.34, P<0.001), FHIT蛋白表达量逐渐降低(H=50.93, P<0.001)。血清叶酸含量与FHIT蛋白表达量呈正相关(r=0.213, P=0.001), 在CINⅠ、CINⅡ/Ⅲ、SCC组中两者均呈现正相加交互作用。细胞试验显示, 随着叶酸浓度增加, 宫颈癌细胞的增殖抑制率(r=0.98, P<0.001)和凋亡率(r=0.99, P<0.001)逐渐增高, FHIT基因CpG岛甲基化程度逐渐减弱, FHIT蛋白的表达量逐渐升高(r=0.97, P<0.001)。结论 叶酸缺乏和FHIT蛋白异常低表达均可增加宫颈癌和癌前病变的发生风险, 两者在宫颈癌变中存在正相加交互作用。
英文摘要:
      Objective To explore the interaction between folate deficiency and aberrant expression related to fragile histidine triad (FHIT) gene in the progression of cervical cancerization. Methods A total number of 80 patients with histological diagnosis of cervix inflammation (CI), 55 cervical intraepithelial neoplasm Ⅰ(CINⅠ), 55 cervical intraepithelial neoplasm Ⅱ/Ⅲ(CINⅡ/Ⅲ) and 64 cervical squamous cell carcinoma (SCC) were included in this study. Levels of serum folate were detected by microbiological assay method and the methylation status of FHIT gene CpG islands was tested by methylation-specific PCR (MSP). FHIT protein levels were measured by Western blot. In vitro, cervical cancer cell lines CaSki(HPV16-positive) was treated with different concentrations of folate. Proliferation and apoptosis of cells, methylation of FHIT gene and the levels of FHIT protein expression were measured in each group. All analyses were performed with SPSS (version 17.0) statistical software. Differences among groups were assessed by chi-square test, Kruskal-Wallis test. Spearman correlation, and the interaction effects were evaluated by additive model. Methods The levels of serum folate (H=59.08, P<0.001) and FHIT protein expression (H=50.93, P<0.001) decreased gradually along with the severity of cervix lesions, while the methylation rates of FHIT gene CpG islands increased (trend χ2=28.34, P<0.001). Both levels of serum folate levels and FHIT protein expression were positively correlated (r=0.213, P=0.001), with an additive interaction seen between them in CINⅠ, CINⅡ/Ⅲ, SCC groups. In vitro, both rates related to proliferation inhibition (r=0.98, P<0.001) and apoptosis (r=0.99, P<0.001) together with the levels of FHIT protein expression (r=0.97, P<0.001) were all increased gradually with the increase of folate concentration while the methylation status of FHIT gene CpG islands all changed from positive to negative gradually. Conclusion Results from our study revealed that both folate deficiency and FHIT protein aberrant low expression might increase the risk of developing cervical cancer and cervix precancerous lesions, and thus play a synergistic action in the progression of cervical cancerization.
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