A higher degree of methylation of the HPV 16 E6 gene is associated with a lower likelihood of being diagnosed with cervical intraepithelial neoplasia.
A higher degree of methylation of the HPV 16 E6 gene is associated with a lower likelihood of being diagnosed with cervical intraepithelial neoplasia.
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DOI：
10.1002/cncr.25511
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发表时间：
2011-03-01
期刊：
影响因子：
6.2
通讯作者：
Johanning, Gary L.
中科院分区：
文献类型：
--
作者：
Piyathilake, Chandrika J.;Macaluso, Maurizio;Alvarez, Ronald D.;Chen, Min;Badiga, Suguna;Edberg, Jeffrey C.;Partridge, Edward E.;Johanning, Gary L.
尽管HPV 16是与子宫颈癌变相关的最常见的HPV基因型，但只有一小部分感染HPV 16的妇女被诊断为子宫颈癌前病变。因此，HPV 16的分子变化而不是感染本身可能是更好的筛查或诊断生物标志物。该研究的目的是评估HPV E6基因启动子和增强子特定区域的甲基化状态是否与诊断为较高级别宫颈上皮内瘤变（CIN 2+）的可能性独立相关。该研究包括75名诊断为CIN 2+或≤CIN 1的HPV 16阳性妇女。应用焦磷酸测序技术对hpv16e6启动子和增强子的6个胞嘧啶鸟嘌呤二核苷酸（CpG）位点的甲基化进行量化。在逻辑回归模型中，CIN 2+（是/否）是因变量，该模型将HPV 16e6基因CpG位点的甲基化程度指定为主要的独立预测因子。所有模型都根据人口统计学、生活方式、已知的宫颈癌风险因素和“抗癌”微量营养素的循环浓度进行了调整。当HPV 16增强子和启动子位点的甲基化程度≥9.5%时，诊断为CIN 2+的几率降低了79% （OR= 0.21; 95% CI, 0.06-0.79； P=0.02）。结果表明，CpG甲基化独立参与HPV-16的生物学以及更高级别CIN的发展。
Even though HPV 16 is the most common HPV genotype associated with cancerous lesions of the cervix, only a fraction of HPV 16 infected women are diagnosed with pre-cancerous lesions of the cervix. Therefore, molecular changes in HPV 16 rather than infections per se may serve as better screening or diagnostic biomarkers. The purpose of the study was to evaluate whether methylation status of specific regions of the HPV E6 gene promoter and enhancer is independently associated with the likelihood of being diagnosed with higher grades of cervical intraepithelial neoplasia (CIN 2+). The study included 75 HPV 16 positive women diagnosed with CIN 2+ or ≤ CIN 1. Pyrosequencing technology was applied to quantify methylation at 6 cytosine guanine dinucleotide (CpG) sites of the HPV 16 E6 promoter and enhancer. CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified the degree of methylation of the CpG sites of the HPV 16 E6 gene as the primary independent predictors. All models were adjusted for demographic, lifestyle, known risk factors for cervical cancer and circulating concentrations of “cancer-protective” micronutrients. The odds of being diagnosed with CIN 2+ was 79% lower when the degree of methylation of the HPV 16 enhancer and promoter sites were ≥9.5% (OR= 0.21; 95% CI, 0.06–0.79; P=0.02). Results suggested that CpG methylation is independently involved in the biology of HPV-16 as well as in the development of higher grades of CIN.
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影响因子：
3.7
作者：
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DOI：
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作者：
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DOI：
10.1158/1940-6207.capr-08-0175
发表时间：
2009-07
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Piyathilake CJ;Macaluso M;Alvarez RD;Bell WC;Heimburger DC;Partridge EE
通讯作者：
Partridge EE