| 王璐,刘学智,任志英,丁玲,南晶,刘春亮,宋志超,冯美娟,杨倩,王金桃.多环芳烃与p16、FHIT基因CpG岛甲基化在宫颈上皮内瘤变中的交互效应[J].中华流行病学杂志,2017,38(8):1113-1117 |
| 多环芳烃与p16、FHIT基因CpG岛甲基化在宫颈上皮内瘤变中的交互效应 |
| Interaction between polycyclic aromatic hydrocarbons and p16,FHIT gene CpG island methylation in patients with cervical intraepithelial neoplasias |
| 收稿日期:2016-12-27 出版日期:2017-08-12 |
| DOI：10.3760/cma.j.issn.0254-6450.2017.08.023 |
| 中文关键词: 宫颈上皮内瘤变 1-羟基芘 抑癌基因 DNA甲基化 交互效应 |
| 英文关键词: Cervical intraepithelial neoplasia 1-hydroxy pyrene Tumor suppressor gene DNA methylation Interaction |
| 基金项目:国家自然科学基金（81473060，81273157，30872166）；国家卫生和计划生育委员会公益性行业科研专项（201402010）；山西省青年科技研究基金（2015021175）；山西省优势和特色重点学科建设项目 |
| 作者 | 单位 | E-mail | | 王璐 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 刘学智 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 任志英 | 030001 太原, 山西省心血管病医院社区健康中心 | | | 丁玲 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 南晶 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 刘春亮 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 宋志超 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 冯美娟 | 030001 太原, 山西医科大学公共卫生学院流行病学教研室 | | | 杨倩 | 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 |
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| 中文摘要: |
| 目的 探讨多环芳烃与p16、FHIT基因CpG岛甲基化在宫颈上皮内瘤变（CIN）中的作用及其交互效应。方法 利用2014年6-12月建立的山西省阳曲县宫颈病变研究队列。包括经病理学确诊的CIN患者169例（CINⅠ86例，CINⅡ/Ⅲ 83例）和正常宫颈（NC）妇女91例。全部研究对象采用高效液相色谱法检测尿液中的1-羟基芘（1-OHP）浓度，甲基化特异性PCR法检测抑癌基因p16、FHIT CpG岛甲基化状态。应用SPSS 20.0软件进行相关资料的Kruskal-Wallis H检验、χ2检验、趋势χ2检验，应用logistic回归模型计算因素与宫颈疾病之间关联强度的OR值及其95%CI，应用广义多因子降维模型（GMDR）评价交互作用。结果 随着CIN程度加重，1-OHP水平逐渐上升（H=50.743，P<0.001），1-OHP高暴露率逐渐升高（趋势检验χ2=20.146，P<0.001）。CINⅠ、CINⅡ/Ⅲ组p16、FHIT CpG岛甲基化率均高于NC组；随着CIN程度的加重，p16基因CpG岛甲基化率（趋势检验χ2=9.75，P=0.002）、FHIT基因CpG岛甲基化率（趋势检验χ2=10.39，P=0.001）均逐渐升高。GMDR交互作用分析显示，在CINⅠ和CINⅡ/Ⅲ组，1-OHP高暴露与p16、FHIT基因CpG岛甲基化呈交互作用。结论 1-OHP高暴露和p16、FHIT CpG岛甲基化均可增加CIN的风险，且在病变中具有协同作用。 |
| 英文摘要: |
| Objective To explore the effect of polycyclic aromatic hydrocarbons (PAHs) and p16, FHIT gene CpG island methylation, as well as their interaction in cervical intraepithelial neoplasias. Methods Objects of this study were from a cohort of cervical lesions study in Yangqu county of Shanxi province. All the patients were diagnosed pathologically, that including 83 patients with high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ), 86 patients with low-grade cervical intraepithelial neoplasia (CINⅠ) and another 91 women under normal cervical (NC) condition. 1-hydroxy pyrene in the urine was detected by high performance liquid chromatography (HPLC) while CpG island methylation status of tumor suppressor gene p16 and FHIT were measured by methylation-specifc polymerase chain reaction (MSP). Data were analyzed with Kruskal-Wallis H test, chi-square test and trend of chi-square test. Logistic regression models were used to estimate the odds ratio (OR) and corresponding 95% confidence intervals (95%CI) between influencing factors and the cervical disease by using the SPSS statistical software (version 20.0). The interaction under study was evaluated by using the generalized multifactor dimensionality reduction (GMDR) model. Results Level of 1-hydroxy pyrene (H=50.743, P<0.001) and the high exposure rate of 1-hydroxy pyrene (trend χ2=20.146, P<0.001) were gradually increasing along with the severity of cervical intraepithelial neoplasia. The CpG island methylation rates of p16, FHIT in CINⅠ and CINⅡ/Ⅲ group were higher than that in NC group, and gradually increasing along with the severity of cervical intraepithelial neoplasia (trend χ2=9.75, P=0.002; trend χ2=10.39, P=0.001). Results from the GMDR model showed that interaction existed among the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16, FHIT in CINⅠ and CINⅡ/Ⅲ group. Conclusion Under the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16, FHIT appeared to have increased the risk of cervical intraepithelial neoplasia and causing synergistic effect in cervical intraepithelial neoplasia. |
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