Fas和Fas配体基因启动子单核苷酸多态性与子宫颈癌的发病风险

Association between Fas/Fas L genes promoter polymorphisms and pathogenic risk of cervical cancer

目的探讨凋亡相关基因Fas和Fas配体（Fas L）启动子区单核苷酸多态与宫颈癌发病风险的关系。方法采用PCR-限制性片段长度多态性方法，检测314例宫颈癌患者和615例正常对照者的外周静脉血Fas-670A／G、Fas-1377G／A和Fas L-844T／C多态位点的基因型。应用多因素Logistic回归分析基因多态与宫颈癌风险的相关性以及与宫颈癌临床病理特征的关系。结果携带Fas L-844CC基因型者患宫颈癌风险较携带Fas L-844TT基因型者增加3.05倍（P〈0.01）；Fas-670A／G和Fas-1377G／A均与宫颈癌发病风险无关；Fas和Fas L基因多态间存在协同作用。分层研究显示，Fas-670G和Fas-1377A等位基因是患宫颈原位鳞癌的危险因素（OR分别为1.77和1.93；P〈0.05）。Fas L-844CC基因型携带者患宫颈浸润性鳞癌的风险较Fas L-844TT基因型携带者增加（OR=3.33；P〈0.01）。Fas和Fas L基因多态与宫颈癌临床分期、细胞分级、肿瘤大小和血清鳞状上皮细胞癌抗原等无关。结论Fas和Fas L基因多态与子宫颈癌遗传易感性相关。

Objective To investigate the association between apoptosis genes Fas/Fas L promoter polymorphisms and the risk of the development of cervical cancer. Methods Blood samples were collected from 314 cases with primary cervical cancer and 615 healthy controls. Genotypes of Fas/Fas L genes were determined by polymerase chain reaction-based restriction fragment length polymorphism. The associations with the risk of cervical cancer and impact of clinicopathological characteristics were estimated by logistic regression. Results Fas L-844CC genotype was significantly associated with increased risk of cervical cancer compared with Fas L-844TC or -TT genotype （ OR = 3.05 ; P 〈 0.01 ）. However, there was no significant difference of Fas-670A/G or -1377G/A genotypes. Interaction of genetic polymorphism between Fas and Fas L was observed. Stratification analysis revealed that Fas-670G or -1377A allele was significantly higher in squamous carcinoma in situ （ OR = 1.77 or 1.93 ; P 〈0.05） while Fas L-844CC genotype had an increased risk of invasive squamous carcinoma compared with that of Fas L-844TT genotype （ OR = 3.33 ; P 〈0.01）. No significant associations were observed between polymorphisms in Fas/Fas L and clinical FIGO stage, cell differentiation, size of tumors, serum squamous cell carcinoma antigen value at the diagnosis and so on. Conclusion The results of this study suggest that genetic polymorphisms of Fas and Fas L in apoptotic pathway are associated with the risk of development of cervical carcinoma.