超过80%女性一生中曾有人乳头瘤病毒（human papilloma virus, HPV）感染，但只有不到4%的感染呈持续性进而发展为宫颈癌前病变和癌，感染者的遗传特征决定了HPV感染转归方向和宫颈癌的临床特征，然而这些遗传特征及与HPV相互作用导致宫颈癌发生、发展的机理目前尚未阐明。宫颈癌家系人群属于极端高发人群，将家系人群纳入研究对象更易找到宫颈癌的遗传特征。我们在前期宫颈癌家系全基因组测序中在一个大家系发现了DLGAP2基因突变，该突变在一代测序得到进一步验证，同时共表达网络分析发现DLGAP2可与DLG2/DLG4相互作用，而后者可与HPV E6结合，从而介导宫颈癌的发生。基于此我们以家系人群为切入点探讨DLGAP2多态性与宫颈癌易感性的关联及与HPV感染、整合、转归等交互分析，并在分子细胞及动物水平进行DLGAP2的作用机理及功能研究，将有助于揭示宫颈癌发生机制及圈定高危人群。

More than 80% of women have HPV infection in their lifetime, but less than 4% of those infected were persistent infection and then developed to cervical intraepithelial neoplasia and cervical cancer. The genetic characteristics of the host play an important role on the occurrence and development of cervical cancer. However, the genetic characteristics of cervical cancer and the mechanism by which the susceptible genes interact with HPV to cause the occurrence and development of cervical cancer have not been elucidated. The incidence of cancer in pedigree population is higher than that in sporadic population, so we can better find tumor susceptibility genes using pedigree population. Based on family WGS, we found DLGAP2 gene mutation in a family. Meanwhile, co-expression network analysis suggested that this gene could bind to DLG2/DLG4, which could bind to HPV E6 protein, thus mediating the occurrence of cervical cancer. So we further plan to explore the association between DLGAP2 polymorphism and cervical cancer susceptibility, as well as the interaction analysis with HPV infection, integration, and reverse, and conduct functional studies on DLGAP2 at the cellular and molecular level and in vivo, which will help to reveal the pathogenesis of cervical cancer and identify high-risk group.