全基因组关联研究确定了多个结直肠癌易感SNP位点，但多数位点位于内含子区、基因间区。如何确定其调控的靶基因和靶基因的功能研究是后续研究的关键。表达数量性状座位(eQTL)分析是解决这一难题的有效手段。我们的前期研究中，对美国国立基因组研究所收录的结直肠易感 SNPs进行eQTL分析，发现全新的肿瘤相关基因CCDC12，其在结直肠癌发生发展中的作用及机制尚无研究。前期研究发现CCDC12基因在癌组织中表达水平显著高于对照癌旁组织；下调CCDC12基因，可以显著抑制肿瘤细胞增殖侵袭；CCDC12基因可能为新的肿瘤相关癌基因。本研究将进行体内体外实验研究CCDC12基因功能，同时利用基因表达芯片和蛋白质芯片寻找其可能的作用靶点或通路，深入探讨其肿瘤相关分子机制。最终为结直肠癌发生分子机制的阐明及寻找有效的治疗靶点提供新的线索。

Since the advent of high-density genotyping arrays, genome-wide association studies (GWAS) have been widely used to identify a number of loci associated with a multitude of disease traits. The vast majority of GWAS tag SNPs located in the intergenic or intronic regions. Identification of genes affected by causal variants and the mechanism by which genotype influences phenotype have been major challenges. In our previous study, we performed expression quantitative trait locus-based analyses (eQTLs) using information provided by the Cancer Genome Atlas and National Human Genome Research Institute in CRC tissues. Analysis of the eQTLs of CRC risk loci resulted in the discovery of one variant that was significantly associated with gene expression (CCDC12). It should be noted that identifying an eQTL provides only indirect evidence of a link between genotype and gene transcription. Previous studies have found that CCDC12 gene expression level in cancer tissue was significantly higher than normal tissue. Silence of CCDC12 gene can significantly inhibit the invasion and metastasis of tumor cells. In present study, we will study the function of CCDC12 gene in vitro and in vivo. Using the gene expression chip and protein chip, we also plan to find its possible target or pathway. This study will elucidate the role and mechanism of CCDC12 affecting the invasion and metastasis of CRC, which might provide the basis for possible new treatment options and ideas.