染色体4q12和17q12区域遗传变异与宫颈癌易感性的关联研究

人乳头瘤病毒（Human papillomavirus, HPV）感染是宫颈癌发生的主要危险因素之一，但仅小部分感染者最终罹患宫颈癌，提示环境和遗传因素共同影响着宫颈癌的发生。最新全基因组关联研究发现，染色体4q12和17q12 区域可能是宫颈癌的重要易感区域，但该区域遗传变异在宫颈癌发生中的具体遗传机制尚未阐明。本研究将拟采用大样本病例对照研究方法，对染色体4q12和17q12区域的遗传变异进行精细作图和分子生物学功能研究： ①探讨染色体 4q12 和 17q12 区域的遗传变异在中国人群宫颈癌发生中的作用，基因-基因、基因与环境暴露之间的交互作用；②探讨相关遗传变异对候选易感基因(如GSDMB、ZPBP2 和 EXOC1)的调控机制。本研究结果将为宫颈癌发生机制的阐明提供理论基础，所发现的遗传标志物可为宫颈癌高危人群的筛查和早诊早治提供科学依据。

Human papillomavirus infection is one of the major risk factors for cervical cancer, while only a small part of infected individuals develop cervical cancer, suggesting that both environmental and genetic factors play important role in cervical cancer pathogenesis. The latest cervical cancer genome wide association study have identified two new susceptibility loci at 4q12 and 17q12 region, however, the exact genetic etiology and mechanisms of cervical cancer in these regions are unclear. In this study, we will conduct fine-mapping study and related molecular biology assays by using a large-sample case-control design: 1. Identify the genetic variations in 4q12 and 17q12 regions related to cervical cancer risk in Chinese population. Detect gene-gene and gene-environmental interactions between genetic variants and related risk factors. 2. Reveal the regulatory mechanisms of the relevant genetic variations of susceptibility genes (such as GSDMB, ZPBP2 and EXOC1). The results of our research could improve understanding of the etiology and mechanisms of cervical cancer development, which in turn is important for early detection, diagnosis and targeted treatment of cervical cancer.