叶酸缺乏和p16基因CpG岛甲基化对宫颈癌变的作用  

Folate deficiency and aberrant methylation of p16 CpG islands on cervical cancer and its precancerous lesions

作　　者：吴婷婷[1] 王金桃[1] 丁玲[1] 樊金荣 李颖[1] 白兰[1] 周芩[1] 

机构地区：[1]山西医科大学公共卫生学院流行病学教研室,山西太原030001 [2]介休市计划生育妇幼保健中心,山西介休032000

出　　处：《中华疾病控制杂志》2013年第1期9-12,共4页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(30872166);山西省自然科学基金(2008011075-1)

摘　　要：目的探讨叶酸缺乏和抑癌基因p16 CpG岛甲基化异常与宫颈癌变的关系,以及两者在宫颈癌变中的相互作用。方法选择经病理学确诊的宫颈鳞状细胞癌(squamous cell carcinoma,SCC)患者85例,宫颈上皮内瘤样变(cervical intraepithelial neoplasm,CIN)患者60例和宫颈组织正常(normal cervix,NC)妇女103例为研究对象,采用放射免疫法检测其血清叶酸水平,宫颈组织中p16基因CpG岛甲基化状况采用甲基化特异PCR检测。结果在NC、CIN和SCC组,血清叶酸的平均水平依次为2.64 ng/ml、2.07 ng/ml和1.72 ng/ml,随着宫颈病变程度的增加,血清叶酸含量逐渐降低,p16基因CpG岛甲基化率逐渐升高(2趋势=32.22,P<0.001)。交互作用分析显示,叶酸缺乏和p16基因CpG岛甲基化异常在宫颈癌的发生发展中存在正相加交互作用。结论叶酸缺乏与p16基因CpG岛甲基化异常均可增加宫颈癌变的风险,且二者在宫颈癌变中存在正相加交互作用。Objective To explore the effect of folate deficiency and CpG islands aberrant methylation of tumor suppressor gene p16 on cervix carcinogenesis and the possible association between them. Methods 85 patients with cervix squamous cell carcinoma （SCC）, 60 patients with cervical intraepithelial neoplasm （CIN）and 103 patients with normal cervix （NC）diagnosed by histology were included in this study. Radioimmunoassay （RIA） and methylation-specific PCR （MSP） were used to detect the levels of serum folate and methylation status of p16 gene CpG islands in cervical tissues, re- spectively. Results The average levels of serum folate were 2. 64 ng/ml, 2. 07 ng/ml and 1.72 ng/ml from NC to SCC group, suggesting that the serum folate levels were descended with the severity of cervix lesions, and methylation rates of （ x^2trend = 32. 22, P 〈 0. 001 ）. Moreover, the results showed that there was an p16 gene CpG islands were increased steadily 2 additive interaction between folate deficiency and methylation status of p16 gene CpG islands in cervix carcinogenesis. Con- clusions Our study revealed that both the deficiency of serum folate and methylation status of p16 gene CpG islands could increase the risk of cervix carcinogenesis and there might be a synergistic action between them.

关 键 词：叶酸 宫颈肿瘤 流行病学 

分 类 号：R181.3[医药卫生—流行病学] R737.33[医药卫生—公共卫生与预防医学]