miR-196a2 T>C基因多态与宫颈癌易感性的关系研究

Polymorphism of the pre-mir-196a2 is associated with susceptibility of cervical cancer in Jiangsu population

目的：探讨mi R-196a2 T〉C基因多态与江苏人群宫颈癌遗传易感性的关系。方法 ：选择经组织学确诊的509例新发宫颈癌患者作为病例组,与病例组人群不存在生物学相关的562例正常人群作为对照组,利用Taqman实时荧光定量PCR技术检测基因型;选择宫颈鳞状细胞癌标本20例,实时荧光定量PCR（RT-q PCR）检测各基因型mi R-196a的表达量;Logistic回归模型计算基因型与人群罹患宫颈癌的风险比（odds ratio,OR）及其95%的可信区间（95%CI）。结果：携带mi R-196a2突变纯合子CC个体罹患宫颈癌的风险明显高于TT基因型个体（OR=1.45,95%CI：1.04~2.09）,携带TC/CC基因型个体增加约33%的宫颈癌发病风险（OR=1.33,95%CI：1.06~1.81）;对宫颈鳞状细胞癌（cervical squamous cell carcinoma,CSCC）分析,与TT基因型比较,含突变纯合子CC个体罹患CSCC的风险明显升高（OR=1.49,95%CI：1.05~2.11）,携带TC/CC基因型个体增加约31%的CSCC发病风险（OR=1.31,95%CI：1.00~1.73）;RT-q PCR显示,在宫颈鳞癌组织中CC及CT/CC基因型与TT基因型相比,成熟mi R-196a的表达水平明显升高。结论 ：Mi R-196a2 T〉C多态变异与中国江苏人群宫颈癌遗传易感性关联密切。

Objective：To study the possible association between mi R-196a2 gene polymorphisms and cervical cancer susceptibility among women in Jiangsu Province. Methods：The subjects included 509 cervical cancer cases and 562 cancer-free controls. We genotyped the functional polymorphism of mi R-196a2（rs11614913）by Taq Man-Probe assay method,and used a sample of 20 cervical cancer tissues to test the expression of mature mi R-196 a by real-time quantitative reverse transcription. Results：When compared with TT genotype,the variant homozygote CC genotype were associated with increased cervical cancer risk（OR=1.45,95%CI = 1.04~2.09）and cervical squamous cell carcinoma（CSCC） risk（OR=1.49,95%CI = 1.05~2.11）; moreover,CC genotype was associated with high mi RNA levels in CSCC tissues,whereas TT genotype showed a relatively low expression in comparison to both TC / CC（P=0.040） and CC patients（P=0.030）. Conclusion：The natural genetic variation in pre-mi R-196a2 may affect the amount of mature mi R-196 a in vivo,and contribute to the susceptibility to cervical cancer.