食管癌候选基因和全基因组关联研究（GWAS）发现并经人群大样本验证了位于9个染色体区段的10多个易感基因及其易感位点。然而，所鉴定的这些常见基因变异的致病分子机理尚不清楚。本研究拟在食管癌候选基因关联研究和GWAS研究的工作基础上，针对两个细胞凋亡与坏死调控基因--CASP8及其异构体和RIP3，采用多阶段表达数量性状位点（eQTL）分析、全蛋白质组水平疾病相关SNP分析（PWAS）、特定环境因素相关的全基因组表观遗传学分析（EWAS）和基因功能研究相结合的方法，分离鉴定易感基因位点特异结合的转录因子及其调控基因、认识后天特定环境因素与易感基因的交互作用，认识食管癌易感基因及其相关位点在食管癌变中的分子机理。

Esophageal cancer is one of the most malignant cancers in China. Esophageal cancer candidate gene and genome-wide association study (GWAS) found that over 10 susceptibility gene located in 9 chromosome segments with different loci and their susceptible sites were confirmed by the crowd large sample validation. However, the identification of these common genetic variants of pathogenic molecular mechanism is unclear. Based on the works, this study we proposed to investigate the molecular mechanism of CASP8 and its isomers and RIP3 expression in tumorigenesis of esophageal cancer through different approaches, e.g. a multi-stage expression quantitative trait loci (eQTL) analysis, proteome-wide analysis of disease associated SNPs (PWAS) and epigenome-wide association study (EWAS). For both apoptosis and necrosis in regulating gene - CASP8 and its isomers and RIP3, we try to identify specific environmental factors related to epigenetics, such as smoking or alcohol drinking by EWAS; and to isolate the specific binding of transcription factors which bound on the susceptibility loci by PWAS respectively. After serious studies of gene function we hope to better understand the interaction of the acquired specific environmental factors and susceptibility genes, understanding the molecular mechanism of esophageal esophageal cancer susceptibility gene and its associated sites.