高危型人乳头瘤病毒(HPV)是导致宫颈癌发生的必要条件，但仅少数持续感染者最终发展为宫颈癌，提示遗传差异可能影响女性感染HPV后的不同结局。有报道显示，HPV E6蛋白能靶向作用于肿瘤坏死因子α(TNF-α)/TNF-α受体1(TNFR1)凋亡信号复合体，保护细胞逃避其介导的凋亡途径。我们前期研究发现TNF-α诱导蛋白8的功能性单核苷酸多态性(SNP)与宫颈癌易感性相关。因此，TNF-α/TNFR1凋亡信号复合物的SNP可能影响高危型HPV的致病性，进而与宫颈癌的易感性相关。本研究通过大样本的病例-对照研究，筛选潜在功能性SNP进行基因型检测，结合高危型HPV感染，研究其与宫颈癌发病风险的相关性，并分析基因-基因/基因-环境交互作用对宫颈癌易感性的影响；同时对阳性关联SNP进行组织学和细胞学功能实验，探讨其与宫颈癌易感性的关联机制；并进行一系列细胞凋亡检测，研究其可能的分子机制。

Cervical cancer is one of the most common cancers among women worldwide. Epidemiological and laboratory-based studies have identified the infection with high-risk HPV types as a necessary but not sufficient cause of cervical cancer. The prevalence of genital HPV infections in developing countries is very high in young women, but most of the infections regress without intervention. Genetic susceptibility may play important roles in the pathogenicity of high-risk HPV. Previous data have identified that HPV E6 oncoprotein can inhibit tumor necrosis factor alpha (TNF-α)/ TNF-α receptor 1 (TNFR1) mediated apoptosis by binding to the death domain of the TNFR1, preventing it from interacting with TRADD and accelerating the degradation of FADD. Single nucleotide polymorphisms (SNPs) in TNF-α/TNFR1 apoptotic complex genes may modulate genomic instability to high-risk HPV infection and contribute to inter-individual diversity in cervical cancer susceptibility. The aim of this relatively large sample-size case-control study is to investigate the associations between potentially functional SNPs in TNF-α/TNFR1 apoptotic complex genes and cervical cancer susceptibility, as well as the effect of gene-gene/ gene-environment (especially with high-risk HPV infection) interactions on cervical carcinogenesis. Further functional experiments and apoptotic detection analyses are performed to clarify the underlying mechanism of this association. This study can give an insight in biological mechanisms of TNF-α/TNFR1 apoptotic complex involving in the development of cervical cancer and may provide biomarkers for the disease risk predication.